Preparation, Characterization and Stability Studies of Glassy Solid Dispersions of Indomethacin using PVP and Isomalt as carriers

Document Type: Original Article

Authors

1 Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Drug Delivery Research Centre, Avicenna Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s)
The purpose of the present study was to use the solid dispersion (SD) technique to improve the dissolution rates of indomethacin (IMC).
Materials and Methods
IMC solid dispersions in PVP K30 and isomalt (GALEN IQ 990) were prepared using the solvent evaporation technique and a hot melt method in weight ratios of 2, 10 and 30% (IMC:PVP). Solid dispersions and physical mixtures were characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and dissolution test. Physical stability tests were also performed at different temperatures and humidity conditions.
Results
The dissolution rates of all solid dispersions were faster than those of their physical mixtures. In samples containing 2% or 10% of IMC, there were no significant differences between the dissolution rates of IMC in PVP and isomalt solid dispersions, but in samples containing 30% of IMC, the dissolution rates were higher in isomalt dispersions. The XRPD analysis showed no crystalline peaks in solid dispersions, indicating that IMC was amorphous within the carrier. The DSC results showed that an interaction occurred between the drug and the carrier in PVP and isomalt dispersions. Physical stability tests at severe storage conditions showed that the dissolution rate of IMC in PVP solid dispersions decreased, while the dissolution profile of IMC in isomalt solid dispersions did not change significantly.
Conclusion
It was shown that the dissolution rates of IMC in PVP and isomalt solid dispersions were substantially increased compared with their physical mixtures and pure IMC.
 

Keywords


1. Lindenberg M, Kopp S, Dressman JB. Classification of orally administered drugs on the World Health Organization Model list of essential medicines according to the biopharmaceutics classification system. Eur J Pharm Biopharm  2004; 58:265-278.

2. Merisko-Liversidge E, Liversidge GG. Nanosizing for oral and parenteral drug delivery: A perspective on formulating poorly-water soluble compounds using wet media milling technology. Adv Drug Deliv Rev 2011; 63:427-440

3. Challa R, Ahuja A, Ali J, Khar RK. Cyclodextrins in drug delivery: an updated review. AAPS PharmSciTech 2005; 6:E329-357.

4. Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today 2007; 12:1068-1075.

5. Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm  2000; 50:47-60.

6. Wang X, de Armas HN, Blaton N, Michoel A, Van den Mooter G. Phase characterization of indomethacin in binary solid dispersions with PVP VA64 or Myrj 52. Int J Pharm 2007; 345:95-100.

7. Fujii M, Okada H, Shibata Y, Teramachi H, Kondoh M, Watanabe Y. Preparation, characterization, and tableting of a solid dispersion of indomethacin with crospovidone. Int J Pharm  2005; 293:145-153.

8. Takeuchi H, Nagira S, Yamamoto H, Kawashima Y. Solid dispersion particles of amorphous indomethacin with fine porous silica particles by using spray-drying method. Int J Pharm  2005; 293:155-164.

9. Sethia S, Squillante E. Solid dispersion of carbamazepine in PVP K30 by conventional solvent evaporation and supercritical methods. Int J Pharm  2004; 272:1-10.

10.  Ndindayino F, Henrist D, Kiekens F, Van den Mooter G, Vervaet C, Remon JP. Direct compression properties of melt-extruded isomalt. Int J Pharm  2002; 235:149-157.

11.  Langer MH, Höltje M, Urbanetz  NA, Brandt B, Höltje HD, Lippold BC. Investigations on the predictability of the formation of glassy solid solutions of drugs in sugar alcohols.Int J Pharm. 2003; 252:167-79.

12.  Costa FO, Sousa JJ, Pais AA, Formosinho SJ. Comparison of dissolution profiles of Ibuprofen pellets. J Control Release  2003; 89:199-212.

13.  Solomon ME. Control of Humidity with potassium hydroxide, sulphuric acid, or other solutions. Bull Entomol Res 1951; 42:543-554.

14.  Craig DQM. The mechanisms of drug release from solid dispersions in water-soluble polymers. Int J Pharm. 2002; 231:131-144.

15.  Shivakumar G. Kapsi a JWA. Processing factors in development of solid solution formulation of itraconazole for enhancement of drug dissolution and bioavailability. Int J Pharm 2001; 229:193-203.

16.  Van den Mooter G, Weuts I, De Ridder T, Blaton N. Evaluation of Inutec SP1 as a new carrier in the formulation of solid dispersions for poorly soluble drugs. Int J Pharm 2006; 316:1-6.

17.  Wang X, Michoel A, Van den Mooter G. Solid state characteristics of ternary solid dispersions composed of PVP VA64, Myrj 52 and itraconazole. Int J Pharm 2005; 303:54-61.