Site Loader
Rock Street, San Francisco

Procedure proof is set uping documented grounds which provides a high grade of confidence that a specific procedure ( such as the industry of pharmaceutical dose signifier ) will systematically bring forth a merchandise meeting its preset specifications and quality features.

The definition is really good thought out each word has a particular significance.

We Will Write a Custom Essay Specifically
For You For Only $13.90/page!


order now

Documented Evidence:

Validation requires a through certification everything that is non documented is considered incomplete.1

High Degree of Assurance:

This confidence is a big package bundle which is used in complex computerized system is seldom free of mistakes. Frequently there is a perceptual experience that proof means “ error free ” . This premise is incorrect. During the proof procedure everything realistically possible should be done to cut down mistakes to a high grade.

Specific Procedure:

Some subparts of proof such as making. ( Design, Installation, Operation, Performance ) are merchandise specific and have to be done for each system.

Systematically:

Validation is non a erstwhile event. The public presentation of equipment has to be controlled during the full life of merchandise.

Predetermined Specification:

Validation activities start with the definition of specifications. The public presentation of equipment is so verified against these specifications. Acceptance standards must be defined prior to testing.2

Reasons for Validation:

The three basic and most of import grounds for proof are choice confidence, economic sciences and conformity.

1. Quality Assurance:

Product quality can non be assured for a procedure by everyday quality control proving because of the restriction of statistical sampling and the limited sensitiveness of finished merchandise testing. Quality fluctuation among units within a batch or among, different batches is rarely detected by proving of finished merchandise samples.

Validation changes the adequateness and dependability of a system or procedure to run into preset standards.

2. Economicss:

The direct economic benefit of proof is a decrease in the cost associated with procedure monitoring, trying and proving. Analysis of multiple samples would non be required in order to decelerate homogeneousness for a validated blending procedure.

The consistence and dependability of a validated procedure to bring forth a quality merchandise supply direct cost salvaging ensuing from a lessening or riddance of merchandise rejections, reworks and retesting. Final release of the batch would be expedited and free of holds and complications caused by drawn-out probes of procedure, or analytical related discrepancies. In add-on merchandise quality ailments and possible merchandise callbacks would be minimized.3

3. Conformity:

GMP requires that a written processs and procedure controls be established to guarantee that the drug merchandises have the “ Identity, Strength, Quality and Purity they purport or are represented to treat. ”

BENEFITS OF VALIDATION:

Decrease of Quality Cost

Through proper proof, the cost of the undermentioned procedure can be optimized.

1 ) Preventive cost is the costs incurred in order to forestall failures and cut down assessment costs.

2 ) Appraisal cost of review, proving and choice rating.

3 ) Internal failure costs.

4 ) External failure costs that associated with a nonconformity status after the merchandise has left the company ‘s ownership.4

B ) Process Optimization

The optimisation of the installation, equipment system and closings etc consequences in a merchandise that meets quality demands at the lowest costs. Trained, qualified people are the cardinal elements in procedure optimisation that consequences in bettering efficiency and productiveness.

C ) Assurance of Quality

Validation and procedure control are the bosom of GMPs. Without validated and controlled procedure it is impossible to accomplish quality merchandises. Hence proof is a cardinal component in guaranting the quality of the product.5

D ) Safety

Validation can besides ensue in increased operator safety. Properly calibrated, validated Instruments and gages used to cut down accident and consequences in safety.

Tocopherol ) Better Customer Quality

Through proper proof, Market callback is avoided which consequences in better client attention and quality of the merchandise.

Goal of Process Validation:

To turn out that the procedure is rugged and consistent.

To understand the procedure parametric quantities and their bounds that affects the merchandise features.

A good understood, successfully validated procedure reduces the dependance on intensive in procedure and finished merchandise testing.6

Types of procedure Validation:

Prospective proof

Coincident proof

Retrospective proof

Revalidation.

Prospective Validation:

Prospective proof involves fabrication, sampling, and proving of proof batches harmonizing to a pre-approved proof protocol.

Validation batches are non released until all batches specified in the protocol have been manufactured, all consequences have been reviewed, and proof studies have been written and approved.

Prospective proof should ever be performed for:

New procedure or merchandise

Merchandises transferred between workss

Changes to bing procedures

Coincident Validation:

Validation batches may be released prior to the completion of the industry of all the batches specified in the protocol and the concluding proof study approved.

More rigorous testing is performed than for the normal batch approved.

An interim blessing on a batch by batch by batch basis.7

Coincident proof should merely be used for bing merchandises where the alteration has a low hazard of impacting critical merchandise features.

Standards to be used to find the acceptableness of attack:

The procedure should be good understood, based on development information and current all-out commercial fabrication experience.

There should be no recent history of repeating jobs impacting critical merchandise features.

The batches are produced infrequently ( e.g. limited market demand ) .

Retrospective Validation:

Retrospective proof establishes documented grounds that a system dose what it is supposed to make based on a reappraisal and analysis of historical information.

It is usually conducted on a merchandise being commercially distributed and is based on accrued production, proving and command informations.

Revalidation

This is nil but the repeat of the whole proof procedure or a specific part of it. It becomes necessary in certain state of affairss. Some of the alterations are as follows.

Changes in beginnings of active Raw stuff makers.

Changes in Raw stuffs.

Changes in Packing Materials.

Changes in procedure e.g. Mixing Time, Drying temperature, and Batch size etc.

Changes in Equipment.

Changes in works Facility.

Monitoring of equipment capablenesss over a period of clip.

PHASES OF QUALIFICATION

The proof of installations, equipment and services is called Qualification. The activities associating to proof surveies may be classified in to three stages.

PhaseI:

Pre-Validation Phase or Qualification Phase which covers all activities associating to merchandise research and development, preparation, pilot batch surveies, Scale up surveies, transportation of engineering to commercial graduated table batches, set uping stableness conditions, storage and handling of finished dose signifiers.

Phase II:

Procedure Validation ( Process Qualification Phase ) designed to verify that all established bounds of critical procedure parametric quantities are valid and that satisfactory merchandises can be produced even under worst instance condition.8

Phase III:

Validation Keeping Phase necessitating frequent reappraisal of all procedure related paperss including proof audit studies to guarantee that there have been no alteration, divergences, failures, alterations to production procedure and that all standard operating Procedures have been followed, including alteration control processs.

Parameters TO BE TESTED FOR VALIDATION WORK

S.NO

Validation Work

Tested for the parametric quantities

1

Forces

Qualification, Responsibilities etc.

2

Buildings

Design, Construction.

3

Servicess

Water, Lightings, Cleaning, Ventilation, Waste, Disposal etc.

4

Equipment

Design, Size, Location, Material of building, Manufacturing drawing, Change parts, Maintenance, Cleaning.

5

Raw Material and Components

Control, Testing Storage, Vendor audit.

6

Procedures

Standard Operating Procedures, Sampling, Yield computation, Microbial taints etc.

7

Packaging, Labeling

Issue of labels, Expiry dating etc.

Good VALIDATION PRACTICES

The procedure of supplying documented groundss that any component of engineering operates as intended and will go on to make so is called “ Validation ” .

Good Validation Practices are controls that furnish the footing for guaranting that appropriate engineering is developed, deployed and maintained in appropriate mode. The conceptual model of good proof patterns every bit good as the inside informations of the control is illustrated in the undermentioned figure.

THE PARADIGM

Technology should run into concern demands

Technology should go on to run into concern demands

Technology should be implemented efficaciously in your Environment

Documentation should be complete and current

Merely qualified staffs to Develop maintain and usage Technology

Appropriate degree of Independent quality Control

Controlled Technology = Validated System

Requirements prior to Validation:

The undermentioned cognition must be available anterior to get downing proof:

Critical procedure parametric quantities and their associated bounds.

Critical merchandise features.

Procedure description.

Equipment and stuffs required

Proposed fabrication processs

Proposed cleansing methods

In -process and finished merchandise testing

Validated analytical methods

Mention to development surveies.

Mention to old proof.

What is a Critical Parameter?

Operation of a critical parametric quantity in the scope instantly beyond the operating scope produces stuff of a important quality.

Critical Parameters

A proven acceptable scope is wider than the normal operating scope and should hold been established during development in support of proof.

PAR allows flexibleness for recovery from mistakes during everyday fabrication.

Edge of failure bounds greatly help in set uping the huskiness of procedure.

If operating scopes are close to border of failure, so extended in-process or finished merchandise testing may be required in add-on to proof.

Planing Validation:

Study types:

A ) Uniformity

B ) Keeping

C ) Reproducibility

D ) Process Capability

Credence Standards:

There are typically tighter than the registered finished merchandise specification.

Planing procedure proof:

Number of batches

For most proof surveies, three back-to-back batches will be used.

More batches may be needed if all critical parametric quantities can non be tested with three batches.

Fewer batches may be applicable for alterations that have a low hazard of impacting critical merchandise features.

Validation procedure does non stop after 3 batches, it continues throughout the life rhythm of the merchandise and must be sporadically evaluated for displacements in public presentation

Bracketing:

A merchandise with multiple strengths or batch sizes can be qualified utilizing bracketing to assist restrict the figure of batches.

For illustration: A dry merchandise holding multiple strength, which differs merely in compacting weight.

Three batches each of the lowest and highest strengths could be used to bracket all intermediated strength.

Alternatively, three batches of the lowest strength, plus one batch of each of the other strength may be acceptable.

Identical equipment:

For pieces of equipment that have been proven to be indistinguishable during IQ / OQ, it is non required to run three batches in each piece of equipment during proof.

For Eg: Granulator, Blending armored combat vehicles, Tableting machines.

A scheme to run at least one batch per piece of equipment would be equal.

Stainless Steel Sampling:

Sample volume should be sufficient to execute all needed analysisA containers for the samples should protect them from any degradation.Headspace in the containers should be minimal, except to let rhenium -suspension when required.Sample size should be representative of the process.Take two modesty samples in instance an probe is required.Sampling technique should be described and calibrated trying device should be used.

Keeping surveies:

The keeping survey should be between one and three batches used.

The figure of batches should be determined by the extent to which merchandise features are affected by keeping clip.

Stability surveies:

Validation batches should be subjected to stableness programme:

To run into regulative committedness and

To roll up informations to back up termination interval, preparation, new site or procedure.9

Protocol:

The protocol should stipulate the followers:

The applicable batch record

A list of processs

Trials and checks to be performed

Required informations to be collected and whys

Pre – determined credence standards

Description of each trial method and its aim

Number of batches to be manufactured

Critical merchandise features

Samples size, location, frequence and figure

Procedure for entering and measuring consequences

Duties.

Executing the protocol:

Prior to executing, the undermentioned must be in topographic point:

Released natural and packaging stuffs

Validated analytical methods for finished merchandise

Forces preparation documented

Approved specification and batch record

Qualified public-service corporations

Approved SOPs or bill of exchange SOPs.

Changes to protocol:

Where a alteration to an approved protocol is required prior to the start of executing, the protocol shall be re – issued as the following version and shall be approved by all the same blessing governments as the original protocol before get downing the proof exercise.10

When a alteration is needed after protocol executing has already begin, either

1 ) .The work shall be discontinued and re-started following blessing of a new, revised protocol.

2 ) .Supplemental certification shall be prepared, approved, and issued that specifies the point in the protocol executing at which the auxiliary certification becomes effectual.

All protocol alteration and auxiliary certification that are issued during proof must be documented in the proof study, including alteration principle.

Failed batches:

If a batch fails credence standards for a ground straight related to the procedure being validated, the root cause must be determined, a alteration made and proof restarted.

If a batch failed for a ground unrelated to the making, it is non necessary to get down once more the principle must be documented.11

If the failure prevents all making informations from being collected, the batch should be replaced.to come

If all information was collected, the batch may non be releasable to the market, but can still be considered valid for the proof.

Example of failed batches where PV is non jeopardized:12

If a batch fails in visual aspect because it has physical taint, but the contamination was determined to come from a natural stuff which is non the ground for the proof, the batch could be used every bit long as the other specifications are met.13

If a spill occurs during treating which prevents all informations from being collected, the batch can be replaced in the proof series.

Failed cleansing proof the merchandise may non be acceptable for release to the market, but the batch may still be acceptable as a proof batch.14

No affair why the failure, all batches must be discussed in the proof study

Validation Report:

The proof study should be approved by the same map as the protocol. The followers should be discussed in the report:15

Summary of validated parametric quantity with scopes.

Discussion of important divergences including failed batches.

Recommended alterations to batch records or processs.

A steadfast decision that the procedure is validated.

Attach executed protocol and executed batch record.

Continued rating:

Once the proof batches are completed, the formal proof terminals.

Whether the procedure is runing as expected is determined by analyzing daily procedure control informations and finished merchandise testing.16

A mechanism besides should be in topographic point to sporadically reexamine the information tendencies to bespeak the demand for re-validation.

The periodic reappraisal should besides include reappraisal of in-process and internal release specification, which may switch with clip or may necessitate to be tightened as the procedure public presentation improves.

Certain procedures for unfertile merchandises such as sterilisation procedures and media fills need to be requalified on a regular basis.1

LITERATURE REVIEW

Rajkumar P.Patil ; ( 2011 ) has explored the apprehension of blend uniformity in the industry of solid unwritten dose signifiers under degree Celsius GMP. He concluded that proving concluding blend uniformity as a suited in-process control may measure and foreground the entrance ingredient batch to batch differences every bit good as the physical fluctuations in different tonss of active stuffs.

Garg R et-al ; ( 2008 ) has described counsel for proof of solid dose signifiers, unfertile merchandises, unwritten solutions and suspensions. They gave an overview on facets of proof in footings of pharmaceutical unit operations, i.e. that single proficient operation that comprises assorted stairss involved in merchandise design and rating.

Chitlange S et-al ; 15 ( 2006 ) provided information on proof of granulation procedure which involved proof of equipments utilized in fabrication of granulation and proof of operation carried out for granulation. It besides validate concluding merchandise for bulk denseness, wet content, atom size distribution etc. successfully formalizing a procedure may cut down the dependance upon intensive inprocess and finished merchandise testing.

Anurags.Rathore, Joseph F.Noferi, and Edward R. Arling from pharmacia corporation, and Gail sofer, Bioreliance ; Peter Watler, Amgen, Inc. ; and Rhona O ‘ Leary, Genentech, Inc

The fast one to treat proof these industry experts argue, is to understand that it is a procedure that stretches through the whole merchandise life rhythm. Some secrets of success: Take a squad attack ; concentrate on the timing of the assorted phases of proof ; avoid some common errors ; and construct your certification as you go.

Thomas p. Garcia, 1, * Simon j. Wilkinson, 2 and Jerry F. Scott2

This article discusses the challenges overcome during the development of a blend sampling technique and the successful proof of the blending for a tablet dose signifier incorporating 2 % active ingredient. Contented uniformity consequences are discussed for three pilot- graduated table and seven commercial- scale batches of tablets. Blend and nucleus content uniformity informations from the pilot- graduated table batch were acceptable. For the initial commercial- graduated table batches, although the tablet nucleus content uniformity consequences were hapless. The blend informations for these batches had really high mean values, but acceptable comparative criterion divergence ( RSDs ) . This suggested that the drug was being preferentially sampled by the stealer. But in a consistent, consistent mode. Extensive testing was performed on a commercial – graduated table development batch to place possible causes of trying mistake. The consequences of this testing helped specify the blend- sampling technique and scheme used to formalize the commixture operation.

Quality direction systems – procedure proof counsel:

“ Quality direction systems – procedure proof counsel ” , originally finalized in 1999, is being republished as “ GHTF/SG3/N99-10: 2004 ( edition 2 ) ” after alteration due to the alterations in ISO 13485:2003, which is utilized in some regulative systems. The procedure proof Guidance has been revised in subdivision 0 through 3.4, figure 1 and Annex B. the alteration can be generalized in two classs: 1 ) column alteration of nomenclature to be consistent with ISO 13485:2003.

Wayne A.Taylor ; described the application of many statistical tools like control charts, capableness surveies, designed experiments, tolerance analysis, robust design methods, failure manner and consequence analysis, trying programs, mistake proofing in proof.

A Andrew W. Jones ; ( 2001 ) discussed how to formalize a procedure by presenting some basic statistical constructs to utilize when analysing historical informations from Batch Records and Quality Control Release paperss to set up specifications and quality properties for an bing procedure.

Dusel-RG et-al ; ( 1997 ) performed nutrient and drug disposal demands sing fabrication procedure proof were discussed including illustrations of different types of certification to carry through the demands of minimum or extended records.

Edwards-CM et Al ; ( 1989 ) have done procedure proof of the fabrication of solid dose signifiers was discussed including protocols, records to be maintained, suitableness of natural stuffs, equipment public presentation making, the figure of proof tallies required and acceptance standards.

AIM & A ; OBJECTIVE

Purpose

The purpose of the present work is to analyze the prospective procedure proof of Lamivudine and Tenofovir Disoproxil Fumarate tablet dose preparation.

Aim

To guarantee merchandise quality in each measure of fabrication

To guarantee consistence of the fabrication operation & A ; duplicability of the procedure

To show the hardiness of the procedure

To guarantee the being of all necessary quality confidence systems within the organisation

To guarantee that forces bring forthing the drug merchandise are decently trained and qualified to bring forth the merchandise

To carry through the demands of cGMP, FDA & A ; WHO guidelines

Plan OF WORK

A A A A A A Process proofs to be carry out for the undermentioned drug Lamivudine and Tenofovir Disoproxil Fumarate tablets 300/300 mg.Three back-to-back batches should be manufactured for the proof

Following work have been designed harmonizing to the maestro fabrication expression.

Preparation of flow chart

2. Fixing the proof protocol which include

Review of making position of equipment and installation

Designation of CPPs and CQAs

Preparation of trying program

Acceptance standards

3.Execution of proof

4. Conformity and rating of the consequences

Drug PROFILE

VIREAD is the trade name name for Tenofovir disoproxil fumarate ( a prodrug of tenofovir ) which is a fumaric acid salt of bis-isopropoxycarbonyloxymethyl ester derived function of tenofovir. In vivo Tenofovir disoproxil fumarate is converted to tenofovir, an acyclic nucleoside phosphonate ( nucleotide ) parallel of adenosine 5′-monophosphate. Tenofovir exhibits activity against HIV-1 contrary RNA polymerase.

IUPAC Name

9 [ ( R ) 2 [ [ Bi [ [ ( isopropoxycarbonyl ) oxy ] methoxy ] phosphinyl ] methoxy ] propyl ] A fumarate ( 1:1 ) .

Molecular expression:

C19H30N5O10P aˆ? C4H4O4

Molecular weight:

635.52.

Structural expression:

VIREADA® ( tenofovir disoproxil fumarate ) Structural Formula Illustration

Tenofovir compound

Coloring material:

White to whitish crystalline pulverization.

Solubility:

13.4 mg/mL in distilled H2O at 25 A°C. It has an octanol/phosphate buffer ( pH 6.5 ) divider coefficient ( log P ) of 1.25 at 25 A°C.

Mechanism of action:

Tenofovir disoproxil fumarate is an acyclic nucleoside phosphonate diester parallel of adenosine monophosphate. Tenofovir disoproxil fumarate requires initial diester hydrolysis for transition to tenofovir and subsequent phosphorylation ‘s by cellular enzymes to organize tenofovirdiphosphate, an obligate concatenation eradicator. Tenofovirdiphosphate inhibits the activity of HIV-1 contrary RNA polymerase and HBV polymers by viing with the natural substrate deoxyadenosine 5’-triphosphate and, after incorporation into DNA, by DNA concatenation expiration. Tenofovir is a weak inhibitor of mammalian DNA polymerases I± , I? , and mitochondrial DNA polymerase I? .

Pharmacokineticss

The pharmacokinetics of Lamivudine have been evaluated in healthy voluntaries and HIV-1 septic persons. Tenofovir pharmacokinetics are similar between these population.

Absorption:

VIREAD is a H2O soluble diesterprodrug of the active ingredient tenofovir. The unwritten bioavailability of tenofovir from VIRED in fasted patients is about 25 % following unwritten disposal of a individual dosage of VIRED 300mg to HIV-1 septic patients in the fasted province, maximal serum concentration ( Cmax ) are achieved in 1.0 A±0.4 hrs.Cmax and AUC values are 0.30 A± 0.09 Aµg.hr/ml, severally.

The pharmacokinetics of tenofovirare dose proportional over a VIRED dose scope of 75 to 600mg and are non affected by perennial dosing.

Distribution:

In vitro binding of tenofovir to human plasma or serum proteins is less than 0.7 and 7.2 % , severally, over the tenofovir concentration scope 0.01 to 25 Aµg/ml. the volume of distribution at steady – province is 1.3 A± 0.6 L/kg and 1.2 A± 0.4 L/kg, following endovenous disposal of tenofovir 1.0 mg/ kilogram and 3.0 milligram / kilogram.

Metamorphosis and riddance:

Lamivudine construction expression:

Gram: pkss2.png

Mechanism of action:

It exerts virustatic consequence against retroviruses by competitively suppressing HIV – RT after intracellular transition of the drug to its action signifier.

Pharmacodynamics of Lamivudine

Lamivudine, normally called 3TC ) is a powerful nucleoside parallel contrary RNA polymerase inhibitor ( nRTI ) . It is marketed by GlaxoSmithKline with the trade name names Zeffix, Heptovir, Epivir, and Epivir-HBV. Lamivudine has been used for intervention of chronic hepatitis B at a lower dosage than for intervention of HIV. It improves the seroconversion of e-antigen positive hepatitis B and besides improves histology theatrical production of the liver. Long term usage of 3TC unluckily leads to emergence of a immune hepatitis B virus ( YMDD ) mutation. Despite this, 3TC is still used widely as it is good tolerated.

Pharmacokineticss:

Absorption

C soap is about 1.28aˆ‰mcg/mL ( individual dosage of 100 milligram ) . T soap is 0.5 to 2aˆ‰h. Absolute bioavailability is about 87 % .

Distribution Less than 36 % protein edge. Vd is about 1.3 L/kg.

Metamorphosis

Metamorphosis of 3TC is a minor path of riddance. The metabolite is trans-sulfoxide metabolite.

Elimination

The bulk is eliminated unchanged in the piss. Average half life is 5 to 7 h. Cl is about 398.5 mL/min.

Lamivudine Adverse Reactions / Lamivudine Side Effectss:

Abdominal hurting, sickness, purging, diarrhea, insomnia, cough, nasal symptoms, arthralgia, musculus hurting, concern, febrility, roseola, alopecia, unease, increased creatininephospholinase, & A ; alanine transaminase, peripheral neuropathy. Rarely rhabdomyolysis, pancreatitis, hepatitis.neutropenia & A ; anemia, ( in combination with Retrovir ) thrombopenia, additions in LFTs & gt ; Paronychia. Angioedema, utricaria & A ; anaphylactiod reaction. Lactic acidosis associated wth terrible megalohepatia & A ; hepatic steatosis.

Precautions:

Warnings Lactic acidosis with megalohepatia and steatosis ( including fatal instances ) has been reported with the usage of 3TC entirely or in combination. Severe acute aggravations of hepatitis B have been reported in patients who have discontinued Lamivudine.

MATERIALS AND METHODS

A. List OF EQUIPMENTS USED:

The major equipment ‘s listed in the procedure proof protocol alteration was used and given in the below tabular array.

S.No

Name of equipment ‘s

Size/ capacity

1.

Multimill

2.

Vibrosifter

3.

Roll compactor

4.

V-blender

75 lit

5.

V-blender

500 lit

6.

Tablet compaction machine

30 station individual traffic circle

7.

Tablet coating machine

Neocoata

B.BATCH DETAILS:

Label claim: Each movie coated tablets containsA LAMIVUDINE AND TENOFOVIR DISOPROXIL FUMARATE tablets 300mg/ 3oomg.

No. of batches: Three

Batch size: The proposed batch size of all the three batch is 1,20000 tablets.

C.LIST OF RAW MATERIALS USED:

Natural stuffs:

Tenofovir disoproxil fumarate.

Lamivudine USP.

Microcrystalline cellulose NF.

Croscarmellose Na EP/BP/NF.

Magnesium stearate NF.

Coating stuffs:

Opadry II white 31 K 58902.

Purified H2O USP

PROCESS FLOW DIAGRAM:

The sequence of fabrication operation was carried out as per the below procedure flow diagram.

Measure 1: winnow

1.1 ) Co-sift Tenofovir disoproxil fumarate, microcrystalline cellulose and Croscarmellose Na through ASTM # 25 mesh and collect in a labeled HDPE membranophone lined with two poly bags

1.2 ) Sift the Mg stearate through ASTM # 60 mesh and collect in a labeled HDPE membranophone lined with two poly bags.

Measure 2: pre-mixing

2.1 ) Load the measure 1.1 stuffs into 75 L v-blender and blend for 20 proceedingss at slow velocity ( 14 revolutions per minute ) .

2.2 ) Load the measure 1.2 stuffs into 75 L v-blender and mix for 7 proceedingss at slow velocity ( 14rpm )

2.3 ) Unload the pre-mix of 2.1 and 2.2 into labelled HDPE container holding dual lined polyethylene bags.

Measure 3: compression and milling

3.1 ) Roll compression the pre-mix ( batch 1, 2, and 3 ) into the roller compactor at roller velocity 12 A± 1 ( 11-13 ) revolutions per minute and plumber’s snake velocity 30 A±10 ( 20-40 ) revolutions per minute.

3.2 ) Remove the mulcts from compacts by through mesh size: # 16.

3.3 ) Roll compact the mulcts collected from sifted through mesh size: # 16 into the roller compactor at roller velocity 12 A± 1 ( 11-13 ) RPM and auger velocity 30 A±10 ( 20-40 ) revolutions per minute.

3.4 ) Mill the measure 3.3 compacts through multimill equipped with 1.5mm screen with knives in forward way at medium slow velocity ( 1500 revolutions per minute ) .

3.5 ) Sift the polished granules through ASTM # 16 mesh.

3.6 ) Mill the measure 3.5 ( # 16 mesh ) retains through multimill equipped with 1.5mm screen with knives in forward way at medium slow velocity ( 1500rpm ) .

3.7 ) Repeat 3.6 measure boulder clay there is no retains on # 16 mesh.

3.8 ) Sift the stuffs step 3.7 through # 60 mesh and cod # 60 meshes above retained granules and # 60 meshes below passed mulcts individually in a container and record the weight.

Note: If the weight of mulcts ( below # 60 mesh ) is more than 28.44kg ( 60 % of the entire intra farinaceous weight ) carry out one more rhythm of compression and factory it.

Measure 4: winnow of excess farinaceous stuffs

Sift together 3TC, microcrystalline cellulose ( avicel ) , microcrystalline cellulose ( ceolus ) and croscarmellose Na through ASTM # 25 mesh.

Measure 5: Blend

Load the decompacted granules of measure 3 and sifted stuffs of measure 4 into 500L V- liquidizer and blend for 20 proceedingss at fast velocity ( 10 revolutions per minute ) .

Measure 6: Lubrication

Sift the Mg stearate through ASTM # 60 mesh and burden into 500L V-blender and mix for 7 proceedingss at fast velocity ( 10rpm ) .

Unload the blend into labelled HDPE containers lined with two clear polyethylene bags.

Measure 7: Compaction

Rotatory imperativeness with “ D ” tooling with

Upper clout:20mm A- 9.5mm, modified capsule form, standard concave with bevelled border with ‘RH80 ‘

Lower clout:20mmA-905mm, modified capsule form, standard concave with bevelled border, Plain clout.

Measure 8: In procedure parametric quantities

1.Average weight ( 30 tablets ) :1200mg A±30mg ( 1170-1230mg )

2.Uniformity of weight:1200mg A±4.0 % ( 1152 -1248mg )

3.Hardness: 190-370N

4.Thickness: 7.00A±0.30mm ( 6.70-7.30mm )

5.Disintergration clip: NMT 25 min

6.Friability: NMT 0.8 % ( On 6.5gm of tablet 100 rotary motions )

Coating

1. Opadry II white 31 k58902-36 milligrams /tablet

2. Purified H2O USP Q

Coating parametric quantities

1.Inlet temperature 45- 65 °C, exhaust:40 -50°C

2.Weight of mean tablet weight gain 3.0 % w/w

RATIONALE FOR SELECTION OF NON-CRITICAL & A ; CRITICAL STEPS & A ; ITS PROCESS PARAMETERS FOR VALIDATION

DISPENSING

Check and guarantee distributing booth is clean & A ; line clearance is given as per current version of standard operating processs

Check & A ; guarantee that balance is calibrated

Check for zero mistake in the balance & A ; guarantee that Lamivudine and Tenofovir disoproxil fumarate drug and all the stuffs i.e. , Excipients are issued as per Batch Fabrication Record

PRE-BLENDING

Check & A ; enter the temperature and comparative humidness in treating country

Check & A ; guarantee visually all the equipment & A ; equipment parts are cleaned and record comments if any

Check and enter the unity of the screens before & A ; after sifting and throughout the processing activity

Carry out sifting and dry commixture as per the Batch Manufacturing Record instructions

This measure involves intermixing of deagglomeration stuffs. The intent of blending is to acquire unvarying mix

Lubrication

This measure involves intermixing of stuffs along with the lubricating agent ( Magnesium stearate )

The intent of lubrication is to guarantee the proper lubrication of the granules and to ease easy flow of the granules

In this measure blending is done for 5mins at 10rpm to acquire proper mix of lubricator

GRANULES BLENDING

This procedure involves intermixing of granules. The intent of blending is to acquire unvarying commixture

The content of uniformity of Lamivudine and Tenofovir disoproxil fumarate in the granules shall be tested with blend severally

Sampling shall be performed in the liquidizer & A ; in the unloaded container to look into the content uniformity

Compaction

This procedure involves compaction of greased granule into tablets

Speed of the machine is a critical procedure variable and besides following parametric quantities are proposed to be studied at different machine velocity at different hardness degrees to formalize the compaction procedure like weight fluctuation, thickness, hardness, crumbliness, decomposition & A ; content uniformity

Hopper survey shall be carried out at mark velocity to measure uniformity of blend throughout the compaction procedure & A ; to turn out that no segregation takes topographic point due to centrifugal force caused by agitation of turret and besides by flow of stuffs from provender clip

Coating

This procedure involves surfacing of the tight tablets

In this procedure the critical stairss to be monitored are Inlet air temperature, spray rate, tablet bed temperature & A ; pan rotational velocity

Description, Coating weight addition, Assay, Related substances & A ; Dissolution were monitored for the alterations of the procedure parametric quantities

5.9. VALIDATION PROCEDURE

Three batches are taken for proof which had to be manufactured as described in the Master Production Document

Record the procedure observation phase by phase & A ; batch wise

Output to be recorded at appropriate phases of the procedure as per Master Production Document

Current versions of standard runing process to be followed

Procedure TO BE VALIDATED:

INFLUENCE MATRIX

The Processes to be validated are decided utilizing influence matrix. The effects of procedure variables on merchandise features are studied and assessed as holding medium, weak and strong influence. The variables holding strong and medium are chosen for proof.

Table 3: The effects of procedure variables on merchandise features

Merchandise Features

Procedure variables

Avg.Wt

Hardness

D.T

Content

Uniformity

Dissolution

Crumbliness

Water content / LOD

Sizing /Milling

Sodium

Sodium

Sodium

Sodium

Sodium

Sodium

Sodium

Pre-lubrication

Sodium

Sodium

Sodium

Second

Sodium

Sodium

Meter

Blending

Sodium

Sodium

Sodium

Second

Sodium

Sodium

Meter

Compaction

Second

Second

Second

Second

Meter

Second

Meter

Coating

Second

Tungsten

Meter

Tungsten

Second

Tungsten

Meter

Strong – Second, Medium – M, Weak – W, Not Applicable – Sodium

Avg. Wt- Average Weight, D.T- Disintegration Time

RESULTS AND DISCUSSION

DISPENSING OF RAW MATERIALS: Batch No. 12LT01

Batch Size

144.00kg

Batch No.

12LT01

S.NO

Ingredients/ specification

Class

Material codification

A.R. NO.

Theoretical qty ( kilogram )

Intra granular:

1.

Tenofovir disoproxil fumarate

36.00

36.36

2.

Microcrystalline cellulose

Avicel PH 112

9.27

8.91

3.

Croscarmellose Na

AC-Di-sol

1.80

1.80

4.

Magnesium stearate

veggie

0.33

0.33

Excess granular:

5.

Lamivudine

36.00

36.02

6.

Microcrystalline cellulose

Avicel PH 112

31.77

31.75

7.

Microcrystalline cellulose

Ceolus KG 802

21.00

21.00

8.

Croscarmellose Na

AC-di-sol

6.84

6.84

9.

Magnesium stearate

Vegetable

0.99

0.99

Coating stuffs

S.No

Ingredients

Material codification

A.R. No

Theoretical qty ( kilogram )

Measure dispensed ( kilogram )

1.

Opadry II white 31 K

6.048

6.048

2.

Purified H2O

27.552

27.552

DISPENSING OF RAW MATERIALS: Batch No. 12LT02

Batch Size

144.00kg

Batch No.

12LT02

S.NO

Ingredients/ specification

Class

Material codification

A.R. NO.

Theoretical qty ( kilogram )

Intra granular:

1.

Tenofovir

Disoproxil

Fumarate

36.00

36.36

2.

Microcrystalline cellulose

Avicel PH 112

9.27

8.91

3.

Croscarmellose Na

AC-Di-sol

1.80

1.80

4.

Magnesium stearate

Vegetable

0.33

0.33

Excess granular:

5.

Lamivudine

36.00

36.02

6.

Microcrystalline cellulose

Avicel PH 112

31.77

31.75

7.

Microcrystalline cellulose

Cellulose KG 802

21.00

21.00

8.

Croscarmellose Na

AC-di-sol

6.84

6.84

9.

Magnesium stearate

Vegetable

0.99

0.99

Coating stuffs

S.No

Ingredients

Material codification

A.R. No

Theoretical qty ( kilogram )

Measure dispensed ( kilogram )

1.

Opadry II white 31 K

6.048

6.048

2.

Purified H2O

27.552

27.552

DISPENSING OF RAW MATERIALS: Batch No. 12LT03

Batch Size

144.00kg

Batch No.

12LT03

S.NO

Ingredients/ specification

Class

Material codification

A.R. NO.

Theoretical qty ( kilogram )

Intra granular:

1.

Tenofovir disoproxil fumarate

36.00

36.36

2.

Microcrystalline cellulose

Avicel PH 112

9.27

8.91

3.

Croscarmellose Na

AC-Di-sol

1.80

1.80

4.

Magnesium stearate

veggie

0.33

0.33

Excess granular:

5.

Lamivudine

36.00

36.02

6.

Microcrystalline cellulose

Avicel PH 112

31.77

31.75

7.

Microcrystalline cellulose

Cellulose KG 802

21.00

21.00

8.

Croscarmellose Na

AC-di-sol

6.84

6.84

9.

Magnesium stearate

Vegetable

0.99

0.99

Coating stuffs

S.No

Ingredients

Material codification

A.R. No

Theoretical qty ( kilogram )

Measure dispensed ( kilogram )

1.

Opadry II white 31 K

6.048

6.048

2.

Purified H2O

27.552

27.552

Procedure Check:

Winnow:

Operation

Tonss

12LT01

12LT02

12LT03

Time taken to sift the Tenoforvir disproxil fumarate, microcrystalline cellulose & A ; croscarmellose Na through mesh size: # 25 mesh

No: a0046 and Mg stearate through mesh size: # 60 mesh no: A0049

I

12 proceedingss

20 proceedingss

12 proceedingss

Two

11 proceedingss

19 proceedingss

16 proceedingss

Three

11 proceedingss

18 proceedingss

15 proceedingss

Pre-mixing:

Operation

Batch

Blending clip

12LT01

12LT02

12LT03

Blending of sifted stuffs of s.no:1,2 & A ; 3 from natural materialA tabular array into 75 L. V-blender at 14 RPM

Blending of Mg stearate in to the above mixture.

I

Two

Three

20 proceedingss

7 proceedingss

20 Minutess

7 proceedingss

20 Minutess

7 proceedingss

20 proceedingss

7 proceedingss

20 proceedingss

7 proceedingss

20 Minutess

7 proceedingss

20 proceedingss

7 proceedingss

20 proceedingss

7 proceedingss

20 Minutess

7 proceedingss

Compaction and milling operation:

Operation

12 LT01

12LT02

12LT03

1 ) Gap between compression rollers

0.5 millimeter

0.5 millimeter

0.5 millimeter

2 ) Roll packing the pre-mix of batch I, II, & A ; III.

Roller velocity: 12 Revolutions per minute

Auger velocity: 30 Revolutions per minute

Time: 30mts

Roller velocity: 12 Revolutions per minute

Auger velocity: 30 Revolutions per minute

Time: 30mts

Roller velocity: 12 Revolutions per minute

Auger velocity: 30 Revolutions per minute

Time: 30mts

3 ) Roll packing the mulcts collected from sifted through mesh size: # 16

Roller velocity: 12 Revolutions per minute

Auger velocity: 30 Revolutions per minute

Time: 30mts

Roller velocity: 12 Revolutions per minute

Auger velocity: 30 Revolutions per minute

Time: 30mts

Roller velocity: 12 Revolutions per minute

Auger velocity: 30 Revolutions per minute

Time: 30mts

4 ) Milling of the compacted stuffs in the s.no.2 & A ; 3 of the above operation by the multimill

Speed:1500 RPM

Screen size:1.5 millimeter

Time: 55 proceedingss

Speed:1500 RPM

Screen size:1.5 millimeter

Time:10 proceedingss

Speed:1500 RPM

Screen size:1.5 millimeter

Time:10 proceedingss

5 ) Sifted the above measure through mesh

Size: # 16

Size: # 16

Size: # 16

6 ) Milling the # 16 retains through the multimill of the above operation

Speed:1500RPM

Screen size:1.5 millimeter

Time:10 proceedingss

Speed:1500RPM

Screen size:1.5 millimeter

Time:10 proceedingss

Speed:1500RPM

Screen size:1.5 millimeter

Time:10 proceedingss

7 ) a ) weight of # 60 mesh retained granules

B ) weight of # 60 mesh passed granules

26.34 kilogram

20.60 kilogram

26.78 kilogram

20.20 kilogram

27.04kg

19.93kg

Switching and blending operation:

Operation

12 LT01

12LT02

12LT03

Blending clip for the screened stuff ( excess granular ) and decompacted intra farinaceous stuff in the 500 L v-blender

20 proceedingss,

Speed: high

20 proceedingss,

Speed: high

20 proceedingss,

Speed: high

Blending clip for the sifted Mg stearate and the above stuffs in to v- liquidizer at a velocity of 10 RPM

7 proceedingss,

Speed: high

7 proceedingss,

Speed: high

7 proceedingss,

Speed: high

Remarks:

The sifting pre-mixing, compression & A ; milling and sifting & A ; intermixing procedure were excuted as per the sanctioned BMR. No divergence and incident was observed during the executing of procedure.

STAGE- Compaction:

The compaction procedure are executed as per the sanctioned BMR. The ideal velocity for 30 station, individual rotary compaction machine throughout the compaction was slow ( 20A±5 RPM ) , where all the in procedure parametric quantities were within the bound. No divergence and incident was occurred during the compaction phase.

Physical parametric quantities of Core Tablets

Parameters

Limit

12LT01

12LT02

12LT03

Description

White to murder white, egg-shaped shaped tablets debossed with ‘RH80 ” on one side and field on the other side.

Complies

Complies

Complies

Average weight

1200 A± 30 milligram ( 1170-1230mg )

1206.6 milligram

1214.9 milligram

1205.8 milligram

Uniformity of weight

1200 milligram i‚± 4.0 % ( 1152 – 1248 milligram )

1180.2 – 1227.7 milligram

1199.8 – 1229.6 milligram

1180.9 – 1228.4 milligram

Hardness

190-370 N

187.0 – 206.0 N

238.0 – 276.0 N

391.0 – 427.0 N

Thickness

7.00 A± 0.30 millimeter ( 6.70 – 7.30 millimeter )

7.31 – 7.38 millimeter

7.09 – 7.21 millimeter

6.64 -6.75 millimeter

D.T

NMT 25 proceedingss

1.45 – 2.02 min

2.21 min – 3.02 min

3.45 – 4.12 min

Crumbliness

NMT 0.8 %

0.12 %

0.09 %

0.049 %

1 ) Film Coating- Batch No. 12 LT001

Lot- I

Observation

Lot-II

Lot- III

Time taken for adding Opadry II white 31k 58902 into purified H2O

12 proceedingss

14 proceedingss

13 proceedingss

Coating operation

Speed of discoloration less steel coating pan ( 1 to 10 RPM )

2.5 RPM

2.5 RPM

2.5 RPM

Atomizing air force per unit area ( 2.0 to 6.0 kg/ centimeter

3.5 kg/ centimeter

3.5kg/ centimeter

3.5 kg/ centimeter

Nozzle size should be 1mm

1 millimeter

1 millimeter

1 millimeter

Inlet temperature 45 c- 65 degree Celsius

55 degree Celsiuss

55 degree Celsiuss

55 degree Celsiuss

No of guns used – 3 nos

3 nos

3 nos

3 nos

Peristaltic pump ( 8 to 40 RPM )

15 RPM

15 RPM

15 RPM

Spray noses distance from tablet bed ( 20 to 25 centimeter )

23 centimeter

23 centimeter

23 centimeter

Distance between each gun ( 17 to 24 centimeter )

20 centimeter

20 centimeter

20 centimeter

Spray rate ( 40-100 g/ min )

57g/ min

57g/ min

57g/ min

Spray noses must be perpendicular to turn overing bed of tablets

perpendicular

perpendicular

Perpendicular

Parameters

Scope

LOT-I

LOT-II

LOT-III

Pan velocity

Ramble oning of all time 1-2 proceedingss at 2 RPM

2 RPM

2 RPM

2 RPM

Inlet temperature

45 C- 65 C

55 degree Celsiuss

55 degree Celsiuss

55 degree Celsiuss

LOD at 800 degree Celsiuss

NMT 2.5 % w/w

After 10 proceedingss drying:2.31

After 15 proceedingss drying:2.03

After 15 proceedingss drying: 2.16

Desired weight construct up

2.75-3.25 %

3.07 %

Rejection measure after review in kilogram

0.86 kilogram

Remark: the surfacing procedure was executed as per the sanctioned BMR. No divergence and incident was observed during the executing of surfacing procedure.

2 ) Film Coating- Batch No. 12 LT002

Lot- I

Observation

Lot-II

Lot- III

Time taken for adding opadry II white 31k 58902 into purified H2O

12 proceedingss

14 proceedingss

13 proceedingss

Coating operation

Speed of discoloration less steel coating pan ( 1 to 10 RPM )

2.5 RPM

2.5 RPM

2.5 RPM

Atomizing air force per unit area ( 2.0 to 6.0 kg/ centimeter

3.5 kg/ centimeter

3.5kg/ centimeter

3.5 kg/ centimeter

Nozzle size should be 1mm

1 millimeter

1 millimeter

1 millimeter

Inlet temperature 45 c- 65 degree Celsius

55 degree Celsiuss

55 degree Celsiuss

55 degree Celsiuss

No of guns used – 3 nos

3 nos

3 nos

3 nos

Peristaltic pump ( 8 to 40 RPM )

15 RPM

15 RPM

15 RPM

Spray noses distance from tablet bed ( 20 to 25 centimeter )

23 centimeter

23 centimeter

23 centimeter

Distance between each gun ( 17 to 24 centimeter )

20 centimeter

20 centimeter

20 centimeter

Spray rate ( 40-100 g/ min )

57g/ min

57g/ min

57g/ min

Spray noses must be perpendicular to turn overing bed of tablets

Perpendicular

perpendicular

Perpendicular

Drying parametric quantities: one time the buildup is achieved

Parameters

Scope

LOT-I

LOT-II

LOT-III

Pan velocity

Ramble oning of all time 1-2 proceedingss at 2 RPM

2 RPM

2 RPM

2 RPM

Inlet temperature

45 C- 65 C

55 degree Celsiuss

55 degree Celsiuss

55 degree Celsiuss

LOD at 800 degree Celsiuss

NMT 2.5 % w/w

After 10 proceedingss drying:2.31

After 15 proceedingss drying:2.03

After 15 proceedingss drying: 2.16

Desired weight construct up

2.75-3.25 %

3.07 %

Rejection measure after review in kilogram

0.86 kilogram

Remark: the surfacing procedure was executed as per the sanctioned BMR. No divergence and incident was observed during the executing of surfacing procedure.

3 ) Film surfacing Batch No. 12 LT003

Lot- I

Observation

Lot-II

Lot- III

Time taken for adding opadry II white 31k 58902 into purified H2O

12 proceedingss

14 proceedingss

13 proceedingss

Coating operation

Speed of discoloration less steel coating pan ( 1 to 10 RPM )

2.5 RPM

2.5 RPM

2.5 RPM

Atomizing air force per unit area ( 2.0 to 6.0 kg/ centimeter

3.5 kg/ centimeter

3.5kg/ centimeter

3.5 kg/ centimeter

Nozzle size should be 1mm

1 millimeter

1 millimeter

1 millimeter

Inlet temperature 45 c- 65 degree Celsius

55 degree Celsiuss

55 degree Celsiuss

55 degree Celsiuss

No of guns used – 3 nos

3 nos

3 nos

3 nos

Peristaltic pump ( 8 to 40 RPM )

15 RPM

15 RPM

15 RPM

Spray noses distance from tablet bed ( 20 to 25 centimeter )

23 centimeter

23 centimeter

23 centimeter

Distance between each gun ( 17 to 24 centimeter )

20 centimeter

20 centimeter

20 centimeter

Spray rate ( 40-100 g/ min )

57g/ min

57g/ min

57g/ min

Spray noses must be perpendicular to turn overing bed of tablets

Perpendicular

perpendicular

Perpendicular

Drying parametric quantities: one time the buildup is achieved

LOT-III

Parameters

Scope

LOT-I

LOT-II

2 RPM

Pan velocity

Ramble oning of all time 1-2 proceedingss at 2 RPM

2 RPM

2 RPM

55 degree Celsiuss

Inlet temperature

45 C- 65 C

55 degree Celsiuss

55 degree Celsiuss

After 15 proceedingss drying: 2.16

LOD at 800 degree Celsiuss

NMT 2.5 % w/w

After 10 proceedingss drying:2.31

After 15 proceedingss drying:2.03

Desired weight construct up

2.75-3.25 %

3.07 %

Rejection measure after review in kilogram

0.86 kilogram

Output rapprochement:

Phase

% Reconciliation

Pre-mix ( 1 )

Limit: 95 % to 100 %

B.NO.

12LT01

12LT02

12LT03

Phase

% output

Blending

Limit: 95 % to 100 %

12LT01

12LT02

12LT03

Compaction

Limit: 94.0 % to 101.0 %

12LT01

12LT02

12LT03

Coating ( stage output )

12LT01

12LT02

12LT03

Coating ( over all output )

Limit: 93.0- 100.0 %

12LT01

12LT02

12LT03

Remark: the output was in the specified bound

Phase: Lubrication ( blend uniformity )

Acceptance standards

All single consequences are within 90.0 – 110.0 % from the absolute mean

RSD-NMT 5.0 %

Batch no.

12LT01

12LT02

12LT03

Sampling location

Lamivudine

Tenofovir

Lamivudine

Tenofovir

Lamivudine

1.

99.1

103.9

102.2

100.6

100.5

2.

100.5

100.8

101.0

99.6

100.6

3.

100.5

101.3

101.2

99.5

100.3

4.

100.1

99.4

99.5

98.5

100.9

5.

99.2

101.6

102.1

98.8

100.8

6.

100.3

98.6

99.7

98.5

100.3

7.

100.6

97.3

101.0

99.4

100.3

8.

99.5

99.1

102.3

99.6

99.9

9.

99.9

99.2

102.5

100.6

101.2

10.

100.2

100.0

102.6

99.0

99.4

11.

98.3

99.5

102.3

100.4

100.8

Minimum %

98.3

97.3

99.5

98.5

99.4

Maximum %

100.6

103.9

102.6

100.6

101.2

Average %

99.8

100.1

101.4

99.5

100.5

Remarks: all single consequences are within 90.0-110.0 % from the absolute mean and % RSD: NMT 5.0 %

Phase: Blending Pooled

Batch No.

12LT01

12LT02

12LT03

S.No

Trial

Consequences

Consequences

Consequence

1

Description

Complies

complies

Complies

2

Designation by HPLC

Complies

Complies

Complies

3

Water content ( by kf )

1.4

2.2

1.7

4

Assay by HPLC each 1200mg farinaceous pulverization contains

Lamivudine

Tenofovir disoproxil fumarate

299.6

99.9

299.2

99.7

305.6

101.9

308.1

102.7

305.6

101.9

2 ) 308.4

102.8

Remarks:

The above consequences of proof batches shows that the blending procedure meets the credence standards and intermixing parametric quantities are suited

Phase: Lubrication ( blend uniformity for pooled )

Acceptance standards

All single consequences are within 90.0 – 110.0 % from the absolute mean

RSD-NMT 5.0 %

Batch No.

12LT01

12LT02

12LT03

Sampling location

Lamivudine

Tenofovir

Lamivudine

Tenofovir

Lamivudine

1.

99.1

103.9

102.2

100.6

100.5

2.

100.5

100.8

101.0

99.6

100.6

3.

100.5

101.3

101.2

99.5

100.3

4.

100.1

99.4

99.5

98.5

100.9

5.

99.2

101.6

102.1

98.8

100.8

6.

100.3

98.6

99.7

98.5

100.3

7.

100.6

97.3

101.0

99.4

100.3

8.

99.5

99.1

102.3

99.6

99.9

9.

99.9

99.2

102.5

100.6

101.2

10.

100.2

100.0

102.6

99.0

99.4

11.

98.3

99.5

102.3

100.4

100.8

Minimum %

98.3

97.3

99.5

98.5

99.4

Maximum %

100.6

103.9

102.6

100.6

101.2

Average %

99.8

100.1

101.4

99.5

100.5

% RSD

0.7

1.76

1.06

0.77

0.51

Phase: BLENDIG POOLED

Batch no.

12LT01

12LT02

12LT03

S.No

Trial

consequences

Consequences

Consequence

1.0

Description

Complies

complies

Complies

2.0

Designation by HPLC

Complies

Complies

Complies

3.0

Water content ( by kf )

1.4

2.2

1.7

4.0

Assay by HPLC each 1200mg farinaceous pulverization contains

3TC

tenoforvirdisoproxilfumarate

299.6

99.9

299.2

99.7

305.6

101.9

308.1

102.7

305.6

101.9

2 ) 308.4

102.8

Remark:

The above consequences of proof batches shows that the blending procedure meets the Acceptance standards and intermixing parametric quantities are suited.

Phase: Compaction

Phase

compaction

Sampling location

Samples at every 10 proceedingss

Measured parametric quantities

Uniformity of dose units via content uniformity

Acceptance standards

Redilypassess standards RSDa‰¤ 4.0 % ,

Mean:90.0-110.0 %

All single consequences: 75.0- 125.0 %

B.NO 12LT01

Lamivudine

Tenofovir

Time Interval

Sample No.

Sample No.

1

2

3

Average

RSD

1

2

3

Average

1.

97.2

99.9

101.2

99.4

2.1

96.1

102.7

102.7

100.5

2.

100.1

99.5

100.5

100.

0.5

101.8

98.4

101.4

100.5

3.

100.3

100.1

99.6

100.00

0.4

101.4

100.8

100

100.6

4.

99.9

100.6

99.4

100

0.6

100.3

102.3

99.6

100.7

5.

96.7

100.1

99.7

98.8

1.9

95.9

102.6

100

99.3

6.

99.9

100.1

99.9

100

0.1

98.5

100

100.2

99.6

7.

99.1

99.1

99.1

99.1

0.00

97.6

100.3

100.3

99.6

8.

96.6

100.8

101.0

99.5

2.5

95.0

100.7

101.7

99.0

9.

99.9

99.9

96.7

98.8

1.9

102.0

9802

95.6

98.6

10.

100.1

99.8

99.7

99.9

0.2

100.0

100.5

100.9

100.5

11.

101.0

100.4

100.6

100.7

0.3

100.7

100.4

100.2

100.3

12

99.0

98.7

102.4

100.0

2.1

100.00

96.5

102.7

99.7

.13

98.9

98.2

98.2

99.0

0.8

98.8

101.4

101.7

100.6

14.

97.7

100.3

101.7

99.9

2.0

95.9

101.9

102.0

99.1

15.

100.3

99.9

97.1

99.1

1.8

101.8

99.2

95.0

98.7

16.

97.2

98.4

99.4

98.3

1.1

98.6

98.8

100.4

99.3

17.

100.3

100.4

100.8

100.5

0.3

98.0

99.4

99.9

99.1

18.

96.9

101.3

101.3

99.8

2.5

95.2

100.5

100.3

98.7

19.

99.7

100.6

99.6

100.0

0.6

97.6

99.7

101.2

99.5

20.

98.4

100.5

100.0

99.6

1.1

101.2

101.8

101.4

101.5

21.

100.9

100.8

100.2

100.6

0.4

Post Author: admin

x

Hi!
I'm Gloria!

Would you like to get a custom essay? How about receiving a customized one?

Check it out