The improved dissolution performance of a post processing treated spray-dried crystalline solid dispersion of poorly soluble drugs

Abstract Context: Solution-mediated transformation has been cited as one of the main problems that deteriorate dissolution performances of solid dispersion (SD). This is mainly attributed by the recrystallization tendency of poorly soluble drug. Eventually, it will lead to extensive agglomeration which is a key process in reducing the dissolution performance of SD and offsets the true benefit of SD system. Here, a post-processing treatment is suggested in order to reduce the recrystallization tendency and hence bring forth the dissolution advantage of SD system. Objectives: The current study investigates the effect of a post processing treatment on dissolution performance of SD in comparison to their performances upon production. Methods: Two poorly soluble drugs were spray dried into SD using polyvinyl alcohol (PVA) as hydrophilic carrier. The obtained samples were post processing treated by exposure to high humidity, i.e. 75% RH at room temperature. The physical properties and release rate of the SD system were characterized upon production and after the post-processing treatment. Results and discussion: XRPD, Infrared and DSC results showed partial crystallinity of the fresh SD systems. Crystallinity of these products was further increased after the post-processing treatment at 75% RH. This may be attributed to the high moisture absorption of the SD system that promotes recrystallization process of the drug. However, dissolution efficiencies of the post-treated systems were higher and more consistent than the fresh SD. The unexpected dissolution trend was further supported by the results intrinsic dissolution and solubility studies. Conclusions: An increase of crystallinity in a post humidity treated SD did not exert detrimental effect to their dissolution profiles. A more stabilized system with a preferable enhanced dissolution rate was obtained by exposing the SD to a post processing humidity treatment.

[1]  S. Qi,et al.  An investigation into the influence of drug-polymer interactions on the miscibility, processability and structure of polyvinylpyrrolidone-based hot melt extrusion formulations. , 2015, International journal of pharmaceutics.

[2]  Siok-Yee Chan,et al.  The characterization and dissolution performances of spray dried solid dispersion of ketoprofen in hydrophilic carriers , 2015 .

[3]  P. Ganesan,et al.  Development, characterization and solubility enhancement of comparative dissolution study of second generation of solid dispersions and microspheres for poorly water soluble drug , 2015 .

[4]  L. S. Taylor,et al.  Phase Behavior of Resveratrol Solid Dispersions Upon Addition to Aqueous media , 2015, Pharmaceutical Research.

[5]  M. Khan,et al.  Comparison of X-ray powder diffraction and solid-state nuclear magnetic resonance in estimating crystalline fraction of tacrolimus in sustained-release amorphous solid dispersion and development of discriminating dissolution method. , 2015, Journal of pharmaceutical sciences.

[6]  H. Syed,et al.  Stability indicating HPLC-UV method for detection of curcumin in Curcuma longa extract and emulsion formulation. , 2015, Food chemistry.

[7]  Jayvadan K Patel,et al.  Revealing facts behind spray dried solid dispersion technology used for solubility enhancement , 2013, Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society.

[8]  J. Aylott,et al.  Real time Raman imaging to understand dissolution performance of amorphous solid dispersions. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[9]  Wei Wu,et al.  Understanding the relationship between wettability and dissolution of solid dispersion. , 2014, International journal of pharmaceutics.

[10]  Wei-guo Dai,et al.  Fundamental aspects of solid dispersion technology for poorly soluble drugs , 2013, Acta pharmaceutica Sinica. B.

[11]  Beom-Jin Lee,et al.  Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs. , 2013, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[12]  Richey M. Davis,et al.  Interplay of degradation, dissolution and stabilization of clarithromycin and its amorphous solid dispersions. , 2013, Molecular pharmaceutics.

[13]  Harsh Chauhan,et al.  Correlating the behavior of polymers in solution as precipitation inhibitor to its amorphous stabilization ability in solid dispersions. , 2013, Journal of pharmaceutical sciences.

[14]  Ping Yang,et al.  Physicochemical characterization of felodipine-kollidon VA64 amorphous solid dispersions prepared by hot-melt extrusion. , 2013, Journal of pharmaceutical sciences.

[15]  A. Sharma,et al.  PREPARATION AND CHARACTERIZATION OF SOLID DISPERSIONS OF CARVEDILOL WITH POLOXAMER 188 , 2013 .

[16]  L. S. Taylor,et al.  Influence of particle size on the crystallization kinetics of amorphous felodipine powders , 2013 .

[17]  Lynne S Taylor,et al.  Crystallization of amorphous solid dispersions of resveratrol during preparation and storage-Impact of different polymers. , 2013, Journal of pharmaceutical sciences.

[18]  Gavin K Reynolds,et al.  Mechanistic insights into the dissolution of spray-dried amorphous solid dispersions. , 2012, Journal of pharmaceutical sciences.

[19]  George Zografi,et al.  Assessing the performance of amorphous solid dispersions. , 2012, Journal of pharmaceutical sciences.

[20]  Lian Yu,et al.  Stability of Amorphous Pharmaceutical Solids: Crystal Growth Mechanisms and Effect of Polymer Additives , 2012, The AAPS Journal.

[21]  N. Sahoo,et al.  Dissolution enhancement of quercetin through nanofabrication, complexation, and solid dispersion. , 2011, Colloids and surfaces. B, Biointerfaces.

[22]  S. Min,et al.  The inhibition effect of high storage temperature on the recrystallization rate during dissolution of nimodipine-Kollidon VA64 solid dispersions (NM-SD) prepared by hot-melt extrusion. , 2011, Journal of pharmaceutical sciences.

[23]  P. J. Rolim-Neto,et al.  Solid dispersion systems for increase solubility : cases with hydrophilic polymers in poorly water soluble drugs , 2011 .

[24]  I. Miroshnyk,et al.  Enhanced Dissolution and Oral Bioavailability of Piroxicam Formulations: Modulating Effect of Phospholipids , 2010, Pharmaceutics.

[25]  David S. Jones,et al.  Physicochemical characterization of hot melt extruded bicalutamide-polyvinylpyrrolidone solid dispersions. , 2010, Journal of pharmaceutical sciences.

[26]  Jing Li,et al.  Formation and characterization of solid dispersions of piroxicam and polyvinylpyrrolidone using spray drying and precipitation with compressed antisolvent. , 2009, Journal of pharmaceutical sciences.

[27]  A. Jørgensen,et al.  Humid storage conditions increase the dissolution rate of diazepam from solid dispersions prepared by melt agglomeration. , 2008, Pharmaceutical development and technology (Print).

[28]  A. Rajabi-Siahboomi,et al.  Crystal growth formation in melt extrudates. , 2007, International journal of pharmaceutics.

[29]  Michael P Sigalas,et al.  Investigation of the release mechanism of a sparingly water-soluble drug from solid dispersions in hydrophilic carriers based on physical state of drug, particle size distribution and drug-polymer interactions. , 2007, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[30]  Chandra Vemavarapu,et al.  Use of Surfactants as Plasticizers in Preparing Solid Dispersions of Poorly Soluble API: Stability Testing of Selected Solid Dispersions , 2006, Pharmaceutical Research.

[31]  P. Stewart,et al.  Understanding agglomeration of indomethacin during the dissolution of micronised indomethacin mixtures through dissolution and de-agglomeration modeling approaches. , 2005, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[32]  Manish K. Gupta,et al.  Hydrogen Bonding with Adsorbent During Storage Governs Drug Dissolution from Solid-Dispersion Granules , 2002, Pharmaceutical Research.

[33]  J. Ayres,et al.  Processing factors in development of solid solution formulation of itraconazole for enhancement of drug dissolution and bioavailability. , 2001, International journal of pharmaceutics.

[34]  T. Viegas,et al.  Measurement of Intrinsic Drug Dissolution Rates Using Two Types of Apparatus , 2001 .