Varsha Pokharkar1, Manisha Kutwal, Leenata Mandpe. 1. Bharati Vidyapeeth University, Poona College of Pharmacy, Department of Pharmaceutics, Erandwane, Pune, Maharashtra, India.
Abstract
OBJECTIVE: Pioglitazone is a thiazolidinedion antidiabetic agent which decreases insulin resistance in the periphery and in the liver, resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. Pioglitazone is insoluble in water and has a low dissolution rate. The objective of the current work was to improve aqueous solubility of pioglitazone by the solid dispersion approach using the spray drying technique. DESIGN: In this study, various hydrophilic polymers such as PVP K17, PVP K30, and HPMC E3 were used to prepare pioglitazone solid dispersion by the spray drying method. MAIN OUTCOME MEASURES: Characterization of solid dispersion included solubility, particle size, surface area analysis, differential scanning calorimetry, infrared spectroscopy, x-ray diffraction, and dissolution test. In vivo hypoglycaemic activity was studied in Swiss albino mice. RESULTS: RESULTS showed that there was significant improvement in solubility and dissolution rate in solid dispersion containing PVP K17 than in that of the pure drug. This in turn resulted in improved pharmacodynamic activity, giving 2 fold mean percentage glucose inhibition as compared to the pure drug; thus the solid dispersion strategy proved to be potentially beneficial for improving the in vivo hypoglycaemic activity of pioglitazone. CONCLUSION: Increase in pioglitazone solubility and in vitro dissolution in solid dispersion was followed by improved in vivo hypoglycaemic activity. LAY ABSTRACT: The aim of the present study was to prepare and evaluate solid dispersion of pioglitazone by the spray drying method. Various hydrophilic polymers were used for preparation of solid dispersion. Pioglitazone is an oral antidiabetic agent effective for reactive hypoglycaemia and aggravated glycaemic metabolism associated with insulin resistance. The prepared solid dispersion was evaluated for saturation solubility, drug content, differential scanning calorimetry, x-ray diffraction, infrared spectroscopy, and stability as per International Conference on Harmonisation guidelines. The glucose-lowering response of the optimized formulation was also studied in Alloxan-induced diabetic Swiss Albino mice. The formulation containing hydrophilic polymers showed a satisfactory drug release pattern compared to the pure drug. Further, when in vivo hypoglycaemic response of pure drug, prepared solid dispersion, and marketed formulation was compared, the optimized solid dispersion batch revealed significant improvement in hypoglycaemic activity. Hence, the present study reveals that the formulation of solid dispersion of pioglitazone with hydrophilic polymer exhibits good release properties as well as in vivo antihyperglycemic activity.
OBJECTIVE:Pioglitazone is a thiazolidinedion antidiabetic agent which decreases insulin resistance in the periphery and in the liver, resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. Pioglitazone is insoluble in water and has a low dissolution rate. The objective of the current work was to improve aqueous solubility of pioglitazone by the solid dispersion approach using the spray drying technique. DESIGN: In this study, various hydrophilic polymers such as PVP K17, PVP K30, and HPMC E3 were used to prepare pioglitazone solid dispersion by the spray drying method. MAIN OUTCOME MEASURES: Characterization of solid dispersion included solubility, particle size, surface area analysis, differential scanning calorimetry, infrared spectroscopy, x-ray diffraction, and dissolution test. In vivo hypoglycaemic activity was studied in Swiss albino mice. RESULTS: RESULTS showed that there was significant improvement in solubility and dissolution rate in solid dispersion containing PVP K17 than in that of the pure drug. This in turn resulted in improved pharmacodynamic activity, giving 2 fold mean percentage glucose inhibition as compared to the pure drug; thus the solid dispersion strategy proved to be potentially beneficial for improving the in vivo hypoglycaemic activity of pioglitazone. CONCLUSION: Increase in pioglitazone solubility and in vitro dissolution in solid dispersion was followed by improved in vivo hypoglycaemic activity. LAY ABSTRACT: The aim of the present study was to prepare and evaluate solid dispersion of pioglitazone by the spray drying method. Various hydrophilic polymers were used for preparation of solid dispersion. Pioglitazone is an oral antidiabetic agent effective for reactive hypoglycaemia and aggravated glycaemic metabolism associated with insulin resistance. The prepared solid dispersion was evaluated for saturation solubility, drug content, differential scanning calorimetry, x-ray diffraction, infrared spectroscopy, and stability as per International Conference on Harmonisation guidelines. The glucose-lowering response of the optimized formulation was also studied in Alloxan-induced diabetic Swiss Albino mice. The formulation containing hydrophilic polymers showed a satisfactory drug release pattern compared to the pure drug. Further, when in vivo hypoglycaemic response of pure drug, prepared solid dispersion, and marketed formulation was compared, the optimized solid dispersion batch revealed significant improvement in hypoglycaemic activity. Hence, the present study reveals that the formulation of solid dispersion of pioglitazone with hydrophilic polymer exhibits good release properties as well as in vivo antihyperglycemic activity.