PREFORMULATION STUDIES FOR THE PREPARATION OF AMORPHOUS SOLID DIS.pdf

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St. John's UniversitySt. John's UniversitySt. John's ScholarSt. John's ScholarTheses and Dissertations2021PREFORMULATION STUDIES FOR THE PREPARATION OFPREFORMULATION STUDIES FOR THE PREPARATION OFAMORPHOUS SOLID DISPERSIONSAMORPHOUS SOLID DISPERSIONSHemanth Kumar MamidiFollow this and additional works at:Part of theOther Pharmacy and Pharmaceutical Sciences Commons
PREFORMULATION STUDIES FOR THE PREPARATION OFAMORPHOUS SOLID DISPERSIONSA dissertation submitted in partial fulfillment of therequirements for the degree ofDOCTOR OF PHILOSOPHYto the faculty of theDEPARTMENT OF PHARMACEUTICAL SCIENCESofCOLLEGE OF PHARMACY AND HEALTH SCIENCESatST. JOHN’S UNIVERSITYNew YorkbyHEMANTH K. MAMIDIDate Submitted:____________________Date Approved:______________________________________________________________Hemanth K. MamidiBhagwan D. Rohera, Ph.D.
© Copyright by Hemanth K. Mamidi 2021All Rights Reserved
ABSTRACTPREFORMULATION STUDIES FOR THE PREPARATION OF AMORPHOUSSOLID DISPERSIONSHemanth K. MamidiThe major challenges in the formulation of amorphous solid dispersions (ASDs)using hot-melt extrusion (HME) are the selection of an ideal polymeric carrier,optimization of HME processing conditions, and screening of the physical stability of theASDs. Addressing these challenges using traditional approaches require extensiveexperimentation and large amounts of active pharmaceutical ingredients (API) whichmay not be feasible during the initial stages of product development. Therefore, there is aneed to develop material-sparing techniques for the successful formulation of ASDs. Theobjective of the present study was to develop material-sparing techniques that can beused as pre-formulation tool during the formulation of ASDs. For this purpose,mefenamic acid (MFA) was used as a model drug and four chemically distinct polymerswith close values of the solubility parameters,viz.Kollidon®VA64, Soluplus®, Pluronic®F68, and Eudragit®EPO, were used as polymeric carriers. The selection of an idealpolymer was carried out based on the solubility parameter approach, melting pointdepression method, thermodynamic phase diagrams, and Gibbs free energy plots. Thenthe HME processing conditions were determined based on a material-sparing techniqueusing differential scanning calorimeter (DSC). The physical stability of the ASDs wasestimated using the modified Avarami equation. Based on the results of the melting pointdepression, thermodynamic phase diagrams and Gibbs free energy plots, Eudragit®EPO
was found to be an ideal polymer for the preparation of amorphous solid dispersionformulation of mefenamic acid. The design space for HME determined using DSCmethod showed that when 20% drug loaded MFA-EPO blends was heated at a rate of 5.5°C/min to a temperature of 146 °C, the resulting ASD contained a residual crystallinity of13.6% and drug degradation of 3.8%. The physical stability of the MFA-EPO ASDsdetermined using a modified Avarami equation showed that the rate of recrystallizationchanged significantly with the change in process temperature as compared to the changein the relative humidity. The study results show that the time frame and experimentsrequired in the formulation of ASDs can be significantly reduced by using the material-sparing techniques developed based on the theoretical and experimental approaches.

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Term
Spring
Professor
N/A
Tags
Polymer, Solubility, The Land, Glass, Differential scanning calorimetry, Glass transition, Amorphous solid

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