Sunday, 24 May 2009

Development and validation of a liquid chromatography-tandem mass spectrometry method for the determination of xanthinol in human plasma

Liu HQ, Su MX, Di B, Hang TJ, Hu Y, Tian XQ, Zhang YD, Shen JP.

Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, PR China.

A sensitive, rapid liquid chromatographic-electrospray ionization mass spectrometric method for the determination of xanthinol in human plasma was developed and validated. Xanthinol nicotinate in plasma (0.5 mL) was pretreated with 20% trichloroacetic acid for protein precipitation. The samples were separated using a Lichrospher silica (5 microm, 250 mm x 4.6 mm i.d.). A mobile phase of methanol-water containing 0.1% formic acid (50: 50, v/v) was used isocratically eluting at a flow rate of 1 mL/min. Xanthinol and its internal standard (IS), acyclovir, were measured by electrospray ion source in positive selected reaction monitoring mode. The method demonstrated that good linearity ranged from 10.27 to 1642.8 ng/mL with r=0.9956. The limit of quantification for xanthinol in plasma was 10.27 ng/mL with good accuracy and precision. The mean plasma extraction recovery of xanthinol was in the range of 90.9-100.2%. The intra- and inter-batch variability values were less than 4.8% and 7.9% (relative standard deviation, R.S.D.), respectively. The established method has been successfully applied to a bioequivalence study of two xanthinol nicotinate tablets for 20 healthy volunteers.

PMID: 18718822 [PubMed - indexed for MEDLINE

Harmonization of strategies for the validation of quantitative analytical procedures: a SFSTP proposal part IV. Examples of application.

Hubert P, Nguyen-Huu JJ, Boulanger B, Chapuzet E, Cohen N, Compagnon PA, Dewé W, Feinberg M, Laurentie M, Mercier N, Muzard G, Valat L, Rozet E.

Laboratory of Analytical Chemistry, Bioanalytical Chemistry Research Unit, Institute of Pharmacy, University of Liège, CHU, B36, B-4000 Liège, Belgium.

A harmonized approach for the validation of analytical methods based on accuracy profile was introduced by a SFSTP commission on the validation of analytical procedure. This fourth and last document aims at illustrating this methodology and the statistics used. Therefore the validation of real case methods are proposed such as methods for the quality control of drugs, for the quantitation of impurities in drug substances, for bioanalysis or for the determination of nutriments. Furthermore, different types of analytical methods are used in order to demonstrate the applicability of the proposed approach to a wide range of methods such as liquid chromatography (LC-UV, LC-MS), spectrophotometry or ELISA.

PMID: 18768284 [PubMed - indexed for MEDLINE

Development and validation of a HPLC method for the analysis of promethazine hydrochloride in hot-melt extruded dosage forms.

Thumma S, Zhang SQ, Repka MA.

Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.

A simple and rapid stability-indicating HPLC method was developed for determination of promethazine hydrochloride (PMZ) in hot-melt extruded (HME) films and sustained release tablets. Chromatographic separation was achieved on a 150 mm x 4.6 mm i.d., 3 microm particle size, C8 (2) column with acetonitrile-25mM phosphate buffer (pH 7.0), 50:50 (v/v) as mobile phase at a flow rate of 1 mL min(-1). Quantitation was achieved with UV detection at 249 nm based on peak area. The method was validated in terms of linearity, precision, accuracy, robustness specificity, limits of detection and quantitation according to ICH guidelines. Specificity was validated by subjecting the drug to acid, base, oxidative, reductive and dry heat degradations. None of the degradation products obtained by forced degradation interfered with the PMZ peak. The method was successfully applied for assessing the stability of the drug in the HME films and sustained release tablet formulations. In addition, uniformity of PMZ content in HME films was also determined using the method developed. Excipients present in either of the dosage forms analyzed did not interfere with the analysis indicating the specificity of the method. Due to its simplicity and accuracy, the method is suitable for application to various dosage forms.

Development and validation of a sensitive LC-MS/MS method with electrospray ionization for quantitation of pramipexole in human plasma

Bharathi DV, Hotha KK, Sagar PV, Kumar SS, Naidu A, Mullangi R.

Bioanalytical Department, Integrated Product Development, Dr Reddy's Laboratories Ltd, Bachupalli, Hyderabad-500 072, India.

A highly sensitive and specific LC-MS/MS method has been developed and validated for the estimation of pramipexole (PPX) with 500 microL human plasma using memantine as an internal standard (IS). The API-4000 was operated under multiple-reaction monitoring mode (MRM) using the electrospray ionization technique. Solid-phase extraction was used to extract PPX and IS from human plasma. The resolution of peaks was achieved with 0.01 m ammonium acetate buffer (pH 4.4):acetonitrile (30:70, v/v) on a Discovery CN column. The total chromatographic run time was 3.0 min and the elution of PPX and IS occurred at approximately 2.32 and 2.52, respectively. The MS/MS ion transitions monitored were 212.10 --> 153.10 for PPX and 180.20 --> 107.30 for IS. The method was proved to be accurate and precise at linearity range of 20-3540 pg/mL with a correlation coefficient (r) of > or =0.999. The intra- and inter-day precision and accuracy values found to be within the assay variability limits as per the FDA guidelines. The developed assay method was applied to a pharmacokinetic study in human volunteers following oral administration of 0.25 mg PPX tablet.

Extended release dosage form of glipizide: development and validation of a level A in vitro-in vivo correlation.

Ghosh A, Bhaumik UK, Bose A, Mandal U, Gowda V, Chatterjee B, Chakrabarty US, Pal TK.

Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, Kolkata-700 032, India.

Defining a quantitative and reliable relationship between in vitro drug release and in vivo absorption is highly desired for rational development, optimization, and evaluation of controlled-release dosage forms and manufacturing process. During the development of once daily extended-release (ER) tablet of glipizide, a predictive in vitro drug release method was designed and statistically evaluated using three formulations with varying release rates. In order to establish internally and externally validated level A in vitro-in vivo correlation (IVIVC), a total of three different ER formulations of glipizide were used to evaluate a linear IVIVC model based on the in vitro test method. For internal validation, a single-dose four-way cross over study (n=6) was performed using fast-, moderate-, and slow-releasing ER formulations and an immediate-release (IR) of glipizide as reference. In vitro release rate data were obtained for each formulation using the United States Pharmacopeia (USP) apparatus II, paddle stirrer at 50 and 100 rev. min(-1) in 0.1 M hydrochloric acid (HCl) and pH 6.8 phosphate buffer. The f(2) metric (similarity factor) was used to analyze the dissolution data. The formulations were compared using area under the plasma concentration-time curve, AUC(0-infinity), time to reach peak plasma concentration, T(max), and peak plasma concentration, C(max), while correlation was determined between in vitro release and in vivo absorption. A linear correlation model was developed using percent absorbed data versus percent dissolved from the three formulations. Predicted glipizide concentrations were obtained by convolution of the in vivo absorption rates. Prediction errors were estimated for C(max) and AUC(0-infinity) to determine the validity of the correlation. Apparatus II, pH 6.8 at 100 rev. min(-1) was found to be the most discriminating dissolution method. Linear regression analysis of the mean percentage of dose absorbed versus the mean percentage of in vitro release resulted in a significant correlation (r(2)>or=0.9) for the three formulations.

PMID: 18827360 [PubMed - indexed for MEDLINE

Rapid and sensitive liquid chromatography-tandem mass spectrometry: assay development, validation and application to a human pharmacokinetic study

Song M, Wang L, Zhao H, Hang T, Wen A, Yang L, Jia L.

Department of Pharmaceutical Analysis, China pharmaceutical University, Nanjing 210009, China.

Rasagiline is a highly potent, selective and irreversible second-generation monoamine oxidase inhibitor with selectivity for type B of the enzyme (MAO-B). The present studies aimed at developing and validating a rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for determination of rasagiline in human plasma and urine. LC-MS/MS analysis was carried out on a Finnigan LC-TSQ Quantum mass spectrometer using positive ion electrospray ionization (ESI(+)) and selected reaction monitoring (SRM). The assay for rasagiline was linear over the range of 0.01-40 ng/mL in plasma and 0.025-40 ng/mL in urine. It took 5.5 min to analyze a sample. The average recoveries in plasma and urine samples were both >85%. The RSD of precision and bias of accuracy were less than 15% and 10%, respectively, of their nominal values based on the intra- and inter-day analysis. The developed method was proved to be suitable for use in clinical pharmacokinetic study after single oral administration of 0.5, 1 and 2 mg rasagiline mesylate tablets in healthy Chinese volunteers.

Development and validation of a high-performance thin-layer chromatographic method, with densitometry, for quantitative analysis of ketorolac trometha

López-Bojórquez E, Castañeda-Hernández G, González-de la Parra M, Namur S.

Fundación Liomont A.C. privada Jesús del Monte 77, Cuajimalpa, Mexico D.F.

Ketorolac tromethamine is a potent nonsteroidal anti-inflammatory drug that is widely used in the treatment of moderate to severe pain. A new method was developed and validated for quantifying ketorolac (the free acid of the tromethamine salt) in human plasma by high-performance thin-layer chromatography. The stationary phase was silica gel 60, and the composition of the mobile phase was n-butanol-chloroform-acetic acid-ammonium hydroxide-water (9 + 3 + 5 + 1 + 2, v/v). The densitometric analysis of ketorolac was performed at 323 nm. The method was validated for precision (repeatability and reproducibility), accuracy, and sensitivity. Repeatability was 10.11% [coefficient of variation (CV)] and reproducibility was 12.18% (CV) as the maximum variation. Accuracy was determined at 3 different concentration levels, and results were within +/-15% of the predetermined range. Data were fitted by a linear mathematical function (linear regression). The calibration graph was linear in the range of 200-2000 ng/mL. Average recovery was 73.67%. The method proved to be accurate, precise, and sensitive for the ketorolac tromethamine quantification.

Development and validation of a reversed-phase HPLC method for simultaneous estimation of ambroxol hydrochloride and azithromycin in tablet dosage for

Shaikh KA, Patil SD, Devkhile AB.

P.G. Department of Chemistry, Sir Sayyed College, P.B. No. 89, Roshan Gate, Aurangabad 431001, M.S., India.

A simple, precise and accurate reversed-phase liquid chromatographic method has been developed for the simultaneous estimation of ambroxol hydrochloride and azithromycin in tablet formulations. The chromatographic separation was achieved on a Xterra RP18 (250 mm x 4.6 mm, 5 microm) analytical column. A Mixture of acetonitrile-dipotassium phosphate (30 mM) (50:50, v/v) (pH 9.0) was used as the mobile phase, at a flow rate of 1.7 ml/min and detector wavelength at 215 nm. The retention time of ambroxol and azithromycin was found to be 5.0 and 11.5 min, respectively. The validation of the proposed method was carried out for specificity, linearity, accuracy, precision, limit of detection, limit of quantitation and robustness. The linear dynamic ranges were from 30-180 to 250-1500 microg/ml for ambroxol hydrochloride and azithromycin, respectively. The percentage recovery obtained for ambroxol hydrochloride and azithromycin were 99.40 and 99.90%, respectively. Limit of detection and quantification for azithromycin were 0.8 and 2.3 microg/ml, for ambroxol hydrochloride 0.004 and 0.01 microg/ml, respectively. The developed method can be used for routine quality control analysis of titled drugs in combination in tablet formulation.

Development and validation of a HPLC method for the determination of buprenorphine hydrochloride, naloxone hydrochloride and noroxymorphone in a table

Mostafavi A, Abedi G, Jamshidi A, Afzali D, Talebi M.

Department of Chemistry, Shahid Bahonar University of Kerman, Kerman, Iran.

A simple isocratic reversed-phase high-performance liquid chromatographic method (RP-HPLC) was developed for the simultaneous determination of buprenorphine hydrochloride, naloxone hydrochloride dihydrate and its major impurity, noroxymorphone, in pharmaceutical tablets. The chromatographic separation was achieved with 10 mmol L(-1) potassium phosphate buffer adjusted to pH 6.0 with orthophosphoric acid and acetonitrile (17:83, v/v) as mobile phase, a C-18 column, Perfectsil Target ODS3 (150 mm x 4.6mm i.d., 5 microm) kept at 35 degrees C and UV detection at 210 nm. The compounds were eluted isocratically at a flow rate of 1.0 mL min(-1). The average retention times for naloxone, noroxymorphone and buprenorphine were 2.4, 3.8 and 8.1 min, respectively. The method was validated according to the ICH guidelines. The validation characteristics included accuracy, precision, linearity, range, specificity, limit of quantitation and robustness. The calibration curves were linear (r>0.996) over the concentration range 0.22-220 microg mL(-1) for buprenorphine hydrochloride and 0.1-100 microg mL(-1) for naloxone hydrochloride dihydrate and noroxymorphone. The recoveries for all three compounds were above 96%. No spectral or chromatographic interferences from the tablet excipients were found. This method is rapid and simple, does not require any sample preparation and is suitable for routine quality control analyses.

PMID: 19084658 [PubMed - in process

evelopment and validation of LC methods with visible detection using pre-column derivatization and mass detection for the assay of voglibose.

Raman NV, Reddy KR, Prasad AV, Ramakrishna K.

Hetero Drugs Ltd. (R&D), Plot No. B. 80 & 81, APIE, Balanagar, Hyderabad 500 018, India.

Two sensitive and selective liquid chromatographic methods were developed for the assay of voglibose (VB) and validated as per International Conference on Harmonization (ICH) guidelines. First method is based on the pre-column derivatization of VB followed by visible detection (LC-VD) and second method involves mass spectrometric detection (LC-MS). In LC-VD method, VB was derivatized with sodium metaperiodate and 3-methyl-2-benzothiazolinone hydrazone hydrochloride monohydrate (MBTH). The derivatized color product of VB (DCPVB) was run through Novapak C18 (300 x 3.9 mm, 4 microm) column using the mobile phase containing buffer (0.01 M mixture of sodium di hydrogen orthophosphate and disodium hydrogen orthophosphate, pH 6.0) and acetonitrile in 35:65 v/v ratio. The eluted DCPVB was monitored at 667 nm. The fixation of optimum conditions in LC-VD method is described. DCPVB structure was confirmed by mass spectral analysis. In LC-MS method, VB was passed through Venusil XBPPH (150 x 4.6 mm, 5 microm) column using a 95:5 v/v mixture of 0.01% formic acid and methanol as mobile phase. The assay concentrations of VB in pure form and in tablets for LC-VD and LC-MS methods are 25 and 5 ngml(-1), respectively.

PMID: 19159812 [PubMed - indexed for MEDLINE

Validation of an age-modified caries risk assessment program (Cariogram) in preschool children.

Holgerson PL, Twetman S, Stecksèn-Blicks C.

Department of Odontology, Faculty of Medicine, Umeå University, Umeå, Sweden.

OBJECTIVES: (i) To validate caries risk profiles assessed with a computer program against actual caries development in preschool children, (ii) to study the possible impact of a preventive program on the risk profiles, and (iii) to compare the individual risk profiles longitudinally. MATERIAL AND METHODS: Caries risk was assessed in 125 two-year-old children invited to participate in a 2-year caries-preventive trial with xylitol tablets. At 7 years of age, 103 were available for follow-up, 48 from the former intervention group and 55 from the control group. At baseline and after 5 years, 7 variables associated with caries were collected through clinical examinations and questionnaires, and scored and computed with a risk assessment program (Cariogram). RESULTS: Children assessed as having a "low chance (0-20%) of avoiding caries" had significantly higher caries at 7 years of age compared to children with a lower risk in the control group (p<0.05)> PMID: 19152150 [PubMed - indexed for MEDLINE

Method for the determination of lycopene in supplements and raw material by reversed-phase liquid chromatography: single-laboratory validation.

Miller A, Pietsch B, Faccin N, Schierle J, Waysek EH.

DSM Nutritional Products Ltd, Research and Development, Analytical Research Center, PO Box 2676, CH-4002 Basel, Switzerland.

A single-laboratory validation study was conducted for a liquid chromatographic (LC) method for the determination of total and all-trans-lycopene in a variety of dietary supplements and raw materials. Gelatin-based and other water-dispersible beadlets, or tablets, capsules, and softgels containing such product forms, were digested with protease. Alginate formulations and the respective applications were treated with an alkaline sodium EDTA acetate buffer to release lycopene from the matrix. Lycopene and other carotenoids were extracted from the resulting aqueous suspensions with dichloromethane and ethanol. Oily product forms were directly dissolved in dichloromethane and ethanol. The extracts were chromatographed on an isocratic high-performance LC system using a C16 alkylamide modified silica column that provided satisfactory resolution of all-trans-lycopene from its predominant cis-isomers and separated the lycopene isomers from other carotenoids such as alpha- and beta-carotene, cryptoxanthin, lutein, and zeaxanthin. The within-day precision relative standard deviation (RSD) for the determination of total lycopene ranged from 0.9 to 5.7% over concentration ranges of 50-200 g/kg for raw materials and 0.3-24 g/kg for dietary supplements. The intermediate precision RSD (total RSD) ranged from 0.8 to 8.9%. Recoveries obtained for beadlet and tablet material for the different extraction variants ranged from 95.0 to 102.1% at levels of 0.02-20 g/kg for tablets and from 95.0 to 101.1% at levels of 1-200 g/kg for beadlet material.

PMID: 19202788 [PubMed - indexed for MEDLINE

Development and validation of RP-HPLC method to determine letrozole in different pharmaceutical formulations and its application to studies of drug re

Mondal N, Pal TK, Ghosal SK.

Department of Pharmaceutical Technology, Jadavpur University, Kolkata-700 032, West Bengal, India.

This study describes development and subsequent validation of a reversed phase high performance liquid chromatographic (RP-HPLC) method for estimation of letrozole, a new aromatase inhibitor, in raw material, pharmaceutical formulations like tablets and nanoparticles and in release medium. The chromatographic system consisted of a FinePak C, column, an isocratic mobile phase composed of deionized water, acetonitrile and methanol (50:30:20 v/v/v) and UV detection at 240 nm. Letrozole was eluted at 9.8 min with no interfering peak of excipients used for the preparation of dosage forms. The method was linear over the range from 1 to 50 microg/mL in raw drug (R2 = 0.9999). The intra-day and inter-day precision values were in the range of 0.122-0.277%. Limit of detection and limit of quantitation were 0.207 microg/mL and 0.627 microg/mL, respectively. Results were validated statistically according to ICH guidelines in both tablets and nanoparticles. Validation of the method yielded good results concerning range, linearity, precision and accuracy. The method was successfully applied in drug release studies from nanoparticles. The release kinetics was found to be fitted into the Higuchi model.

PMID: 19226963 [PubMed - indexed for MEDLINE

Validated method for determination of mazindol in human plasma by liquid chromatography/tandem mass spectrometry.

Kim SS, Lee HW, Lee KT.

College of Pharmacy, Kyung-Hee University, Hoegi-Dong, Dongdaemun-Gu, Seoul 130-701, Republic of Korea.

A simple liquid chromatography/tandem mass spectrometry (LC/MS/MS) method with electrospray ionization in positive ion multiple reaction monitoring mode was developed for the quantification of mazindol (an anorectic agent) in human plasma. Fluoxetine was adopted as an internal standard (IS), and sample preparation involved one-step liquid/liquid extraction using ethyl acetate. The transition monitored were m/z 285>44 for mazindol and m/z 310>44 for IS. Chromatographic separation was achieved on a Capcell Pak MGII C(18) column using an isocratic mobile phase, consisting of acetonitrile-20mM ammonium formate in water (50:50, v/v, adjusted to pH 3.5 with formic acid) at a flow-rate of 0.2mL/min. The retention times of mazindol and fluoxetine were 1.03min and 1.45min, respectively. The lower limit of quantitation (LLOQ) was 0.1ng/mL using 200microL of plasma, and no interferences were detected in chromatograms. The bench top stability of mazindol was evaluated in buffered and non-buffered plasma. The selectivity, linearity, precision, accuracy, recovery, and stability of the devised method were fully validated and absolute and relative matrix effects were evaluated. The described method provides a fast and sensitive analytical tool for determining mazindol levels in plasma, and was successfully applied to a pharmacokinetic study in 24 healthy human subjects after oral administration of 2mg tablet formulation of mazindol under fasting conditions.

PMID: 19272843 [PubMed - indexed for MEDLINE

determination of aspirin and clopidogrel in combined tablets in the presence of degradation products formed under ICH-recommended stress conditions.

Validated column high-performance liquid chromatographic method for determination of aspirin and clopidogrel in combined tablets in the presence of degradation products formed under ICH-recommended stress conditions.

Saurashtra University, Department of Chemistry, Rajkot-360 005, Gujarat, India.

The development and validation of a column high-performance liquid chromatographic assay method for the determination of aspirin and clopidogrel in tablet formulation are described. The combination formulation was subjected to International Conference on Harmonization-recommended stress conditions. Separation of the drugs from the degradation products formed under stress conditions was achieved on an octasilyl (C8) column using 0.3% orthophosphoric acid-acetonitrile (65 + 35, v/v) mobile phase. The method was validated for specificity, linearity, limits of detection and quantification, precision, accuracy, and robustness. The method was found to be specific against placebo interference and during the forced degradation. The response was linear in the concentration range of 30.0-120.0 microg/mL for aspirin and 15.0-60.0 microg/mL for clopidogrel, with a correlation coefficient of 0.9999 for both. The relative standard deviation values for intra- and interday precision were <2.0%.>

PMID: 19382573 [PubMed - in process]

Validation of tablet dissolution method by high-performance liquid chromatography.

Guo JH, Harcum WW, Skinner GW, Dluzneski PR, Trumbull DE.

Hercules Incorporated, Wilmington, DE 19808, USA.'

Dissolution is a qualitative and quantitative tool that can provide valuable information about biological availability of a drug, as well as batch-to-batch consistency. It is considered one of the most important quality control tests performed on pharmaceutical dosage forms, and validation of dissolution methods is an important part of good manufacturing practices (GMP). Hydroxypropylcellulose (HPC) was formulated with acetaminophen (APAP) and hydrochlorothiazide (HCTZ). Dissolution methods and limits are reported in the USP/NF. Standard operating procedures (SOP) for the HP 8452A spectrophotometer and Vanderkamp 600/6010 Dissolution Tester were followed according to the GMP Manual. A dissolution method was developed for each formulation based on the above. The only discrepancy between high-performance liquid chromatography (HPLC) and standard dissolution testing occurred when comparing the results of the HPC/HCTZ formulation. The ultraviolet (UV) samples were filtered through a 10-micron filter, and the HPLC samples were filtered through a 0.2-micron filter. When the HPC/HCTZ samples were filtered through a 10-micron filter for both UV and liquid chromatography (LC), the results were equal. Filter pore size and area have a large effect on concentration of HPC/HCTZ. The smaller the pore size and the smaller the diameter of the filter, the more HPC/HCTZ is filtered out. HCTZ has a greater tendency to interact with HPC in the filter than other active ingredients tested. HPC and HCTZ levels have little or no effect on the amount of HCTZ lost.

PMID: 10738651 [PubMed - indexed for MEDLINE]

Tablet Process Development and Validation and the Application of QbD

The goal of this workshop is to provide detailed information on the implications of Quality by Design (QbD) for the validation and qualification of tablet manufacturing processes and process development. We will also review the principles of PAT for tablets and capsules and their implications for process control, and introduce important new concepts including the use of risk and process matrices for risk management

By the end of the course, you will understand the relationship between QbD principles and tablet development and process validation, understand the processes commonly used to manufacture tablets and capsules, and the factors which affect them, recognise how to identify critical processing parameters, and how to incorporate into a process validation program and understand the principles of PAT, how and where it can be most effectively deployed

Who should attend

Tablet formulation and process development staff and those involved in managing process development and validation, and commissioning products into production. Regulatory Affairs staff preparing dossiers for tablet products. Quality Assurance personnel responsible for the design or implementation of tablet process validation protocols. Numbers will be limited to give participants the opportunity for thorough discussion of the issues to be covered by the programme and one on one consultation with speakers.

Organized by:
PharmaTraining Services
Invited Speakers:
To be advised

Deadline for Abstracts:
Not applicable


Batch size increase without perfoming a process validation


For your question there is no guidlines , But if your equipment have a capacity to increase the batch size then you can increase up to 150 kg but for regulatory purpose you have to do process validation
As per u r question with out process validation on temperory basis u can changate the batch size. but it is permenent basis u must be conduct the process validation.

As per u r question with out process validation on temperory basis u can changate the batch size up to 20%. but it is permenent basis u must be conduct the process validation.
Answered By: Rizwan Kazmi PhD |
There is a SUPAC guide line for any change which is not similar to the validated batch with regards to material in the formula, equipment and process

what is the meanning of master validation plan & how we take stepwise proceding

Answered By: George micheal | 2 years ago
Planning is the most important part of computer validation. Having a good plan in place with owners, deliverables and check points makes validation easy. A master plan increases the efficiency and consistency of validation and answers the inspector's question: what is your approach towards computer system validation. A master plan is also a requirement of European GMPs. A validation project plan guides validation professionals through the entire validation process from writing specifications to system retirement. However, despite of this importance, the regulated industry is unsure on how to develop and document such planning.

Regarding Process validation of tablet manufacturing?

In tablet manufacturing process, during validation can we do the process with out fixing the limit for process control parameters for example dry the granules till LOD or Moisture content achieved and vary the RPM of compression machine? Also can we continue the tablet compression with out waiting for blend report and initially compressed tablet dissolution analytical report can we collect these data like during validation and then fix the parameters after the validation based on validation batch results?

Expecting an expert opinion.


Integrated Tablet Formulation Development

please email if you are interested in this course

Integrated Tablet Formulation Development

and Tablet Process Development and Validation

Course Dates: 28, 29 & 30 April 2009 POSTPONED to October/November

Venue: to be advised

Cost: any 1 day - £600.00, any 2 days £1160.00, 3 days £1584.00

Speaker: Dr Michael Gamlen

This unique 3 day course introduces and integrates the key elements of tablet development based on the principles of Quality by Design (QbD) set out in ICH Q9:

  • Preformulation studies
  • Formulation development
  • Process development and validation

and explains the important links between each of these. Proper integration of these elements is essential to achieve “Quality by Design” because data from each phase of development is used to control the next step in the development process. By achieving proper integration based on sound scientific principles, many development and production problems can be avoided. The course includes case studies of tablet development at the preformulation and formulation development phases as well a detailed, step by step analysis of all elements of the tablet manufacturing process. Key process parameters and their control are identified.

Who will benefit from the course?
The course is designed for people new to tablet and process development, and those requiring a refresher in the area. It will also benefit Process Development experts wishing to extend their understanding of why processes can go wrong, and regulatory and quality personnel who need to understand the development process.


Registration and coffee are available each day from 8.30am and course proper starts at 9.15am

Day 1: Preformulation
9.00 Welcome and introductions

9.10 Introduction to preformulation for product development

10.00 Coffee

10.30 Preformulation studies in context

* Making use of your data

11.30 Material Characterisation techniques (1)

12.30 Lunch

14.00 Material Characterisation techniques (2)

14.45 Tablet components and their roles

15.30 Tea

16.00 Excipient compatibility testing

16.45 Case study - applying preformulation in tablet formulation

17.50 Close

18.00 Evening reception

Day 2: Tablet formulation - an introduction

9.00 Introduction to tabletting operations

10.30 Coffee

11.00 Tabletting operations (cont'd)

11.30 Tablet formulation development

12.30 Lunch

13.45 Formulation development case study

14.30 Formulation development case study (2)

15.15 Tea

15.30 Compression testing and use of the Precision Compression Tester

16.30 Preparation for formal stability testing

17.00 Q and A

17.30 Close

16.00 Evening reception

Day 3: Process development and validation
9.00 Workshop introduction

9.20 Quality by design - the basis for process development and validation

10.30 Coffee

11.00 Key Manufacturing processes - purpose, equipment and control (1)

* Blending and lubrication

* Dry Granulation - Roller compaction and slugging

* Wet Granulation

* Granulation end-point control

12.15 Discussion, Review and Q & A

12.30 Lunch

13.30 Case study - blending for direct compression, implementation of recent FDA guidance on blend

sampling. We follow the development of a formulation from hand filled capsules to production tablet

manufacture, reviewing blending options and actual results, and examine the effect of FDA guidance

on blend sample

15.00 Key manufacturing processes - purpose, equipment and control (2)

* Drying

* Sieving

* Tablet compression

* Film coating

16.30 Process control case study - granulation end-point control

* Developing a self-controlling process

17.15 Course ends

18.00 Evening reception

Additional Resources:
An extremely comprehensive memory stick will be provided containing extensive resources on preformulation and tablet formulation, as well as colour copies of all presentations and case studies

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