Formulation and Evaluation of Mucoadhesive Microspheres of Pioglitazone Hydrochloride Prepared by Ionotropic External Gelation Technique

Nagarajan  Sriram; Prakash  Katakam

doi:10.4236/jeas.2016.61003

Nagarajan Sriram¹, Prakash Katakam²^*

Abstract: Microspheres containing Pioglitazone hydrochloride were prepared by the ionotropic external gelation method, using sodium alginate with four mucoadhesive polymers namely sodium carboxy methyl cellulose, hydroxy propyl methyl cellulose, carbopol 934 P and cellulose acetate phthalate as coat materials. Ionotropic gelation is a method to prepare microspheres using combination of Ca²⁺ as cationic components and alginate as anion. The practical yield of prepared microspheres using the ionotropic gelation technique was between 172 mg and 604 mg. The result of the Chi-squared test carried out between the actual (practical) and expected (theoretical) yields showed no significant difference (P < 0.05) which indicated that the ionotropic gelation technique could be successfully employed to prepare pioglitazone microspheres using sodium alginate, sodium carboxy methyl cellulose, carbopol 934 P, HPMC, cellulose acetate butyrate polymers. The drug entrapment efficiency of prepared microspheres showed between 56.12% ± 3.86% to 84.68% ± 2.93% which was significantly higher for ionotropic gelation technique. The highest drug entrapment was found in formulation PMI 8. Swelling index is the capability of a polymer to swell before the drug is released which influences the rate and mechanism of drug release from the polymer matrix. The swelling index of prepared microspheres was in the range of 68% ± 4.52% to 87% ± 0.98%. Pioglitazone HCl microspheres showed controlled release of drug without initial peak level achieving. This type of properties in Pioglitazone HCl microspheres used to decrease side effects, reduce dosing frequency and improve patient compliances. From the all batches PMI 8 is considered the best formulation, because among all other formulations, it shows better extent of drug release up to 82.12% (18 h), good entrapment efficiency (84.68%) and the ex-vivo wash-off test shows the best mucoadhesive property. The in vitro drug release studies do up to 18 h. As observed from the various plots, most of the formulations followed the Korsmeyer-Peppas model.

Keywords: Diabetes Mellitus, Mucoadhesive Microspheres, Mucoadhesive Polymers, Mucoadhesion, Sustained Release, Ionotropic External Gelation Technique

Cite this paper: Sriram, N. and Katakam, P. (2016) Formulation and Evaluation of Mucoadhesive Microspheres of Pioglitazone Hydrochloride Prepared by Ionotropic External Gelation Technique. Journal of Encapsulation and Adsorption Sciences, 6, 22-34. doi: 10.4236/jeas.2016.61003.

References

[1] Liu, Z., Lu, W., Qian, L., Zhang, X., Zeng, P. and Pan, J. (2005) In Vitro and in Vivo Studies on Mucoadhesive Microspheres of Amoxicillin. Journal of Controlled Release, 102, 135-144.
http://dx.doi.org/10.1016/j.jconrel.2004.06.022

[2] Wattamwar, M., Ratnaparkhi, M.P., Kutmalge, M.D. and Jadhav, A.N. (2014) Formulation and in Vitro Evaluation of Mucoadhesive Microspheres of Pioglitazone Hydrochloride. Asian Pacific Journal of Health Sciences, 1, 177-192.

[3] Thompson, C.J., Hansford, D., Higgins, S., Rostron, C., Hutcheon, G.A. and Munday, D.L. (2007) Evaluation of Ibuprofen-Loaded Microspheres Prepared from Novel Copolyesters. International Journal of Pharmaceutics, 329, 53-61.
http://dx.doi.org/10.1016/j.ijpharm.2006.08.019

[4] Thanoo, B.C., Sunny, M.C. and Jayakrishnan, A. (1992) Cross-Linked Chitosan Microspheres: Preparation and Evaluation as a Matrix for the Controlled Release of Pharmaceuticals. Journal of Pharmacy and Pharmacology, 44, 283-286. http://dx.doi.org/10.1111/j.2042-7158.1992.tb03607.x

[5] Patil, S., Babbar, A., Mathur, R., Misha, A. and Sawant, K. (2015) Mucoadhesive Chitosan Microspheres of Carvedilol for Nasal Administration. Journal of Drug Targeting, 18, 321-331.
http://dx.doi.org/10.3109/10611861003663523

[6] Nadigoti, J., Dharani, S., Shayeda and Yamsani, M.R. (2011) Formulation and Evaluation of Floating Microparticles of Metoprolol Succinate. Asian Journal of Pharmaceutical and Clinical Research, 4, 132-135.

[7] Sabitha, P., Vijayaratna, J. and Reddy, K.R. (2010) Design and Evaluation of Controlled Release Chitosan-Calcium Alginate Microspheres of Anti-Tubercular Drugs for Oral Use. International Journal of Chemtech Research, 2, 88-98.

[8] Mitra, A. and Dey, B. (2011) Chitosonmicropheres in Novel Drug Delivery Systems. Indian Journal of Pharmaceutical Sciences, 73, 355-366.

[9] Xu, J., Bovet, L. and Zhao, K. (2008) Taste Masking Microspheres for Orally Disintegrating Tablets. International Journal of Pharmaceutics, 359, 63-69.
http://dx.doi.org/10.1016/j.ijpharm.2008.03.019

[10] Al-Kassas, R.S., Al-Gohary, O.M.N. and Al-Faadhel, M.M. (2007) Controlling of Systemic Absorption of Gliclazide though Incorporation into Alginate Beads. International Journal of Pharmaceutics, 341, 230-237.
http://dx.doi.org/10.1016/j.ijpharm.2007.03.047

[11] Gaba, P., Singh, S. and Gaba, M. (2011) Galactomannan Gum Coated Mucoadhesive Microspheres of Glipizide for Treatment of Type 2 Diabetes Mellitus: In Vitro and in Vivo Evaluation. Saudi Pharmaceutical Journal, 19, 143-152.
http://dx.doi.org/10.1016/j.jsps.2011.02.001

[12] Jose, S., Prema, M.T., Chacko, A.J., Thomas, A.C. and Souto, E.B. (2011) Colon Specific Chitosan Microspheres for Chronotherapy of Chronic Stable Angina. Colloids and Surfaces B: Biointerfaces, 83, 277-283.
http://dx.doi.org/10.1016/j.colsurfb.2010.11.033

[13] Maravajhala, V., Dasai, N., Sepuri, A. and Joginapalli, S. (2009) Design and Evaluation of Niacin Microspheres. Indian Journal of Pharmaceutical Sciences, 71, 663-669.
http://dx.doi.org/10.4103/0250-474X.59549

[14] Gangadhar, B.C., Shyam Sundar, R., Varma, V.K., Sleeva Raju, M. and Sai Kiran, M. (2010) Formulation and Evaluation of Indomethacin Microspheres Using Natural and Synthetic Polymers as Controlled Release Dosage Forms. International Journal of Drug Discovery, 2, 8-16.
http://dx.doi.org/10.9735/0975-4423.2.1.8-16

[15] Liggins, R.T. and Burt, H.M. (2001) Paclitaxel Loaded Poly (L-Lactic Acid) Microspheres: Properties of Microspheres Made with Low Molecular Weight Polymers. International Journal of Pharmaceutics, 222, 19-33.
http://dx.doi.org/10.1016/s0378-5173(01)00690-1

[16] Shah, P., Rajshree, M. and Rane, Y. (2007) Stability Testing of Pharmaceuticals—A Global Perspective. Journal of Pharmacy Research, 6, 1-9.

[17] Stability Testing Guidelines (2003) Stability Testing of New Drug Substances and Products. ICH—Technical Coordination, EMEA, London.

[18] Prakash, K., Raju, P.N., Shanta, K.K. and Lakshmi, M.N. (2007) Preparation and Characterization of Lamivudine Microspheres Using Various Cellulose Polymers. Tropical Journal of Pharmaceutical Research, 6, 841-847.
http://dx.doi.org/10.4314/tjpr.v6i4.14668