Design and Optimization of Pioglitazone Hydrochloride Self-Nanoemulsifying Drug Delivery System (SNEDDS) Incorporated into an Orally Disintegrating Tablet.

Mahmoud Teaima,Fares Alanazi,Mohammed El-Nabarawi,Sandra Hababeh,Doaa Alshora,Mai Khanfar

doi:10.3390/pharmaceutics14020425

Abstract

Pioglitazone Hydrochloride (PGZ) suffers from poor aqueous solubility. The aim of this research was to design orally disintegrating tablets with self-nanoemulsifying properties (T-SNEDDS) to improve the Pioglitazone solubility and dissolution rate. Three liquid self-nanoemulsifying systems (L-SNEDDS) were formulated and evaluated for transmittance percentage, emulsification time, particle size, Poly dispersity index (PDI), percentage of content, solubility and stability. The optimum L-SNEDDS formula was converted to a solidified self-nanoemulsifying drug delivery system (S-SNEDDS) by adsorption on Syloid (SYL). Powder characterization tests, such as flowability tests, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM), were performed for the selected S-SNEDDS formulation. Orally disintegrating tablets (ODT) were formulated by blending S-SNEDDS with tableting excipients. The ODT tablet batch composed of Prosolv was selected for tablet quality control tests, such as hardness, friability, disintegration time, content uniformity, weight variation, in vitro release, in vivo studies and accelerated stability studies. ODT tablets showed accepted mechanical properties and rapid disintegration time (<30 s). No drug degradation was observed at 3 months into the accelerated stability study. The optimized L-SNEDDS, S-SNEDDS and ODT (T-SNEDDS), showed significant enhancement of PGZ in vitro dissolution profiles compared to the pure drug (p > 0.05). In vivo pharmacokinetic and pharmacodynamic evaluation of ODTs showed better behavior compared to the raw drug suspension and the commercial tablet (p > 0.05). Orally disintegrating tablets revealed a promising potential to improve Pioglitazone poor aqueous solubility, dissolution profile and bioavailability.

Highlights

The highest Pioglitazone Hydrochloride (PGZ) solubility was attained by Caproyl 90 with a value of 44.69 mg/mL and Capmul MCM with a value of 32.93 mg/mL
During the development of L-SNEDDS, psuedoternary diagram data revealed that wider phase regions in system I > system II > system III indicated a better self-emulsification ability [37], this was attributed to the required hydrophilic lipophilic balance (RHLB)
Twelve PGZ liquid SNEDDS formulations were developed in this study

Summary

Introduction

Pioglitazone HCl (PGZ) is an antidiabetic drug with an insulin-sensitizing effect. It binds to peroxisome proliferator-activated receptor gamma (PPAR-γ) that increases the transcription of insulin-responsive genes, improves tissue sensitivity towards insulin. PGZ is classified as class II under the biopharmaceutics classification system (BCS), meaning it is poorly soluble and highly permeable. Its poor aqueous solubility (0.015 mg/mL) has been a major constrain that hinders its dissolution rate, resulting in therapeutic level failure [1]. Its poor aqueous solubility (0.015 mg/mL) has been a major constrain that hinders its dissolution rate, resulting in therapeutic level failure [1]. 4.0/).

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