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ENHANCED PERFORMANCE DISSOLUTION OF POORLY WATER SOLUBLE MODEL DRUGS UTILIZING A NOVEL SPRAY-FREEZING INTO LIQUID (SFL) AND ATMOSPHERIC FREEZE DRYING (ATMFD) TECHNOLOGY

IP.com Disclosure Number: IPCOM000114771D
Publication Date: 2005-Mar-29
Document File: 2 page(s) / 434K

Publishing Venue

The IP.com Prior Art Database

Abstract

Micropraticles of API(s) stabilized with excipient(s) have been prepared via a novel particle engineering technology, spray freezing into liquid (SFL) and isolated by atmospheric freeze-drying (ATMFD). The SFL-ATMFD processed materials achieved significantly higher dissolution rates than the micronized API or physical mix.

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ENHANCED PERFORMANCE DISSOLUTION OF POORLY WATER SOLUBLE MODEL DRUGS UTILIZING A NOVEL SPRAY-FREEZING INTO LIQUID (SFL) AND ATMOSPHERIC FREEZE DRYING (ATMFD) TECHNOLOGY

Jonathan C. Evans*, Brian D. Scherzer, James E. Hitt, Gary B. Kupperblatt, and Edmund J. Elder

The Dow Chemical Company, Midland, MI 48674

*email address of presenting author: jcevans@dow.com

ABSTRACT SUMMARY

Micropraticles of API(s) stabilized with excipient(s) have been prepared via a novel particle engineering technology, spray freezing into liquid (SFL) and isolated by atmospheric freeze-drying (ATMFD).  The SFL-ATMFD processed materials achieved significantly higher dissolution rates than the micronized API or physical mix.

Keywords:  microparticles, super critical fluids, surface modification, dissolution, thermal analysis, tablets, polyvinylpyrrolidone

INTRODUCTION

A novel particle engineering technology, spray freezing into liquid (SFL) has been developed that utilizes the atomization of a co-solvent feed solution containing an API and dissolution enhancing excipient(s) directly into a cryogenic liquid, such as nitrogen1.  The liquid-liquid collision between the feed solution and cryogenic liquid results in intense feed jet breakup into fine microdroplets, which solidify almost instantaneously into microparticles. 

The microparticles consist of drug and excipient(s) molecularly dispersed within a matrix of frozen solvent.  The volatile components of this microparticle then are removed via freeze-drying.  This can be accomplished by standard lyophilization or by atmospheric freeze-drying (ATMFD). Atmospheric freeze-drying (ATMFD) a technology that involves the sublimation of frozen solvent(s) from a micronized SFL powder by fluidizing the powder with cryogenic dry airor nitrogen2.  The nitrogen is cooled prior to entering the fluid bed, where the nitrogen will fluidize the frozen SFL powder and sublime the solvent(s) to obtain the dry micronized SFL powder.  The ATMFD process is easily scaleable and affordable, so it is a superior alternative to lyophilization. The resulting dried powder is composed of discrete microparticles where the API is molecularly dispersed within a porous polymeric matrix.

The objective of this study is to demonstrate the use of SFL for enhancing drug dissolution.  The SFL powders were dried by both lyophilization and ATMFD.  The SFL micronized powders and tablets prepared from SFL-ATMFD will be compared to bulk micronized API and a physical mix.

EXPERIMENTAL METHODS

·         Materials

The model API, micronized danazol USP, and the excipients pluronic F-127 and polyvinylpyrrolidone (PVP) K-10 were purchased from Sigma Chemical Co. (St. Louis, MO) and Aldrich Chemical (Milwaukee, WI) respectively.  Reagent grade t-butanol and HPLC grade tetrahydrofuran (THF) were purchased from Fisher Scientific (Fair Lawn, NJ).  Disintegrants employed in tablet preparation include microcrystalline cellulose (AvicelÒ PH101) and croscarmellose sodium (Ac-D...