Choice of Better Laboratory Technique for the Preparation

Choice of Better Laboratory Technique for the Preparation of Microspheres Applying Analytical Hierarchy Process: A Case Study OTECH - 8 P. Venkatesan Lecturer , Annamalai university Annamalainagar 608002 Tamilnadu, India

Choice of Better Laboratory Technique for the Preparation of Microspheres Applying Analytical Hierarchy Process: A Case Study P. Venkatesan 1*, C. Muralitharan 2, R. Manavalan 1 and K. Valliappan 1 Annamalai university, Annamalainagar, Tamilnadu, India.

OBJECTIVE The objective of the case study is to select an appropriate technique that would deliver the quality product with reproducibility of release profile and consistency with good entrapment efficiency by applying Analytical Hierarchy Process (AHP) technique.

INTRODUCTION Microencapsulation is a process by which relatively thin coatings are applied to small particles of solids or droplets of liquids and dispersions. They usually have particle size ranging from several tenths of a micron to 5000 micron

APPLICATIONS • This technology has been used widely in the design of controlled release and sustained release dosage forms. • To mask the bitter taste of drugs like Paracetamol, Nitrofurantoin etc. • To • A reduce gastric and other G. I. tract irritations. liquid can be converted to a pseudo-solid handling and storage. eg. Eprazinone. • To for easy provide protection to the core materials against atmospheric effects, e. g. Vit. A. Palmitate.

METHODS OF MICROENCAPSULATION § § § Air Suspension Coating Thermal Change Incompatible Polymer Addition Non-Solvent Addition Salt Addition Polymer-Polymer Interaction Multi orifice - Centrifugal Process Solvent Evaporation Spray Drying and Spray Congealing Pan Coatings Coacervation Phase Separation.

ANALYTIC HIERARCHY PROCESS (AHP) Analytical Hierarchy Process developed by Thomas L. Saaty is one of the very effective Multi criteria decision making (MCDM) Model. This has been employed very successfully in many situations where a decision situation is characterized by a multitude of complementary and conflicting factors.

Saaty’s nine-point comparison scale Intensity of importance Definition Explanation 1 Equal importance Two activities constitute equally to the objective 3. Moderate importance Experience and judgment of one over another slightly favour one activity over another 5. Essential or strong importance Experience and judgment strongly favour one over another Very strongly demonstrated An activity is favoured very strongly over importance another; its dominance demonstrated in practice 7. 9. 2, 4, 6, 8 Absolute importance Intermediate values between adjacent scale values The evidence favouring one activity over another is of highest possible order of affirmation When compromise is needed Reciprocals of If activity i has one of the above non zero numbers assigned to it when above non zero compared with activity j, then j has the reciprocal value when compared with i

METHODOLOGY AND EXPERIMENTAL WORK The case study was conducted with an objective to choose the better technique between four alternatives, namely Solvent Evaporation (SET), Coacervation Phase Separation (CAP) Pan Coatings (PAN) Spray Drying and Spray Congealing (SPR) for carrying out microencapsulation.

Overall objective Identify relevant criteria Identify alternatives to be rated Develop matrix of pair wise comparison of Calculate normalized weights of criteria Calculate consistency ratio (CR) of pairwise comparison matrix IS CR 0. 10 NO yes

Develop matrix of pairwise alternatives with respect to each Calculate normalised weights of alternatives consistency ratio of pair wise comparison of alternatives Choose a the next IS CR 0. 10 NO yes Have alternatives been compared yes Calculate the overall weight of each alternative Choose the best alternative NO yes NO

1. Process Information [PI] Production scale [PS] Lab scale, Pilot scale, Industrial scale Process condition [PC] Temperature, Stirring speed, Ph 2. Operation Skill [OS] Technique Microencapsulation is a process where by small discrete [MET] solid particles or liquid droplets are surrounded and enclosed by an intact shall Knowledge [KN] Refers to Microencapsulation theoretical background Training [TR] Hands on training on instrument Availability [AV] How easily the machine can be procured. Experience [EX] Reputation of the Supplier Service [SE] Serving and maintenance facilities Spares [SP] Availability of spare parts Monopoly [MO] Vendor status single/Multi Vendor 3. Supplier [SUP]

4. Technical information [TEI] Literature [LT] Scientific Journal, News, magazines updating current trends Manual [MA] Operational and service manual. Establish Technique [ET] Standing of the technique in the global level research Growth [GH] Growth in the field of encapsulation technique Versatility [VE] Operational Flexibility, RPM, Encapsulation Complexity [CO] Complexity of the machine how easily one can handle the instrument 5. Technical Status [TES] 6. Machine [MAC]

Using the AHP model the priority weights, [PR_WT], to the attributes and sub-attributes are calculated by pair wise comparison matrix Evaluation criteria C 1 C 2 C 3. . . C 1 1 Reciprocal of entries below the diagonal C 2 Degree of preferences of C 2 versus C 1 1 C 3 versus C 2 1 Cm C 3 versus C 1 Cm versus C 2 Cm versus C 3. . . Cm 1

RESULTS AND DISCUSSION In the case study, AHP technique was applied to make choice amongst alternative microencapsulation techniques (SET/CAP/PAN/SPR) and thereby opt the best technique. The composite score is used for the final ranking of the alternatives. The solution of the problem involves finding the composite score that reflects the relative priorities of all the alternatives at the lowest level of the hierarchy.

PR_WT Notation PR_WT PS Attributes Subattributes SUP 0. 25 0. 591 0. 247 0. 049 PS 0. 75 0. 559 0. 323 0. 058 PC 0. 455 0. 558 0. 263 0. 056 MET 0. 455 0. 558 0. 263 0. 056 KN TR Supplier SPR KN OS PAN MET Operation skill PI CAP PC Process Information SET 0. 090 0. 469 0. 063 TR AV 0. 334 0. 530 0. 311 0. 096 AV EX 0. 333 0. 450 0. 049 EX SE 0. 111 0. 450 0. 049 SE SP 0. 111 0. 450 0. 049 SP MO 0. 111 0. 438 0. 081 MO 0. 421 0. 261 0. 153

PR_WT Notation PR_WT Subattributes PR_WT LT Attributes Composite score 0. 520 0. 297 0. 124 LT 0. 750 0. 520 0. 297 0. 124 MA 0. 833 0. 638 0. 230 0. 055 0. 073 0. 167 0. 638 0. 230 0. 055 0. 073 0. 750 0. 535 0. 327 0. 091 0. 044 CO MAC 0. 250 VE Machine SPR GR TES PAN ET Technical status TEI CAP MA Technical information SET 0. 250 0. 535 0. 327 0. 091 0. 044 0. 521 0. 305 0. 064 0. 076 0. 094 0. 046 0. 025

It is seen here that, PI is most important (priority = 0. 421) followed by OS (priority = 0. 261) and so on. In the next level of comparison, sub-attributes are compared with each other with respect to an attribute at a higher level. For instance, within PI the sub-attributes PS, PC are compared. Similarly in all the other sub-attributes are compared. The composite score favored the selection of SET (score=0. 5216) over CAP (score=0. 3059), PAN (score=0. 0645), SPR (score=0. 0769) for microencapsulation technique

CONCLUSION In today competitive scenario, an effective framework for selecting a technique for the preparation of microspheres using AHP as MCDM tool is presented in this case study here. This approach is a systematic one and it includes both quantitative and qualitative factors. Software for computing priority weights can be easily developed else commercial software (expert choice) is available.

The factors considered here are illustrative only and these may vary from case to case. The proposed approach can be extended to other situations like selection of alternatives such as tablets formulation machines, characterization technique like pharmacokinetic studies, release behavior, drug content, etc.

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