Eudragit-based nanosuspension of poorly water-soluble drug: formulation and in vitro-in vivo evaluation.

Abstract

The present study was performed to investigate potential of Eudragit RLPO-based nanosuspension of glimepiride (Biopharmaceutical Classification System class II drug), for the improvement of its solubility and overall therapeutic efficacy, suitable for peroral administration. Nanoprecipitation method being simple and less sophisticated was optimized for the preparation of nanosuspension. Physicochemical characteristics of nanosuspension in terms of size, zeta potential, polydispersity index, entrapment efficiency (% EE) and in vitro drug release were found within their acceptable ranges. The size of the nanoparticles was most strongly affected by agitation time while % EE was more influenced by the drug/polymer ratio. Differential scanning calorimetry and X-ray diffraction studies provided evidence that enhancement in solubility of drug resulted due to change in crystallinity of drug within the formulation. Stability study revealed that nanosuspension was more stable at refrigerated condition with no significant changes in particle size distribution, % EE, and release characteristics for 3 months. In vivo studies were performed on nicotinamide-streptozotocin-induced diabetic rat models for pharmacokinetic and antihyperglycaemic activity. Nanosuspension increased maximum plasma concentration, area under the curve, and mean residence time values significantly as compared to aqueous suspension. Oral glucose tolerance test and antihyperglycaemic studies demonstrated plasma glucose levels were efficiently controlled in case of nanosuspension than glimepiride suspension. Briefly, sustained and prolonged activity of nanosuspensions could reduce dose frequency, decrease drug side effects, and improve patient compliance. Therefore, glimepiride nanosuspensions can be expected to gain considerable attention in the treatment of type 2 diabetes mellitus due to its improved therapeutic activity.

• Authors: Sarita Kumari Yadav, Shivani Mishra, Brahmeshwar Mishra
• Journal: AAPS PharmSciTech (AAPS PharmSciTech) Vol. 13 Issue 4 Pg. 1031-44 (Dec 2012) ISSN: 1530-9932 [Electronic] United States
• PMID: 22893314 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hypoglycemic Agents
• Polymers
• Polymethacrylic Acids
• Sulfonylurea Compounds
• Suspensions
• Water
• methylmethacrylate-methacrylic acid copolymer
• glimepiride

Topics

• Animals
• Chemistry, Pharmaceutical (methods)
• Diabetes Mellitus, Experimental (drug therapy)
• Diabetes Mellitus, Type 2 (drug therapy, metabolism)
• Drug Stability
• Female
• Glucose Tolerance Test (methods)
• Hypoglycemic Agents (administration & dosage, chemistry, pharmacokinetics, pharmacology)
• Male
• Nanoparticles (chemistry)
• Particle Size
• Polymers (chemistry)
• Polymethacrylic Acids (chemistry)
• Rats
• Solubility
• Sulfonylurea Compounds (administration & dosage, chemistry, pharmacokinetics, pharmacology)
• Suspensions (chemistry, pharmacokinetics, pharmacology)
• Water (chemistry)