Effect of Solutol HS 15 in Solid Dispersions of Pioglitazone Hydrochloride: in vitro and in vivo Evaluation

Abstract

Poor aqueous solubility and slow dissolution rate adversely affects bioavailability of pioglitazone hydrochloride. This study was undertaken to improve dissolution and bioavailability of pioglitazone hydrochloride through preparation of stable solid dispersions by melting and solvent evaporation method using Solutol HS 15. Solubility of pioglitazone hydrochloride was enhanced by 9 to 49 fold as the drugcarrier ratio was increased in solid dispersions as compared to pure drug. Furthermore, compared to pure drug or physical mixture, solid dispersions significantly improved the dissolution rate and the extent of drug release. Solid dispersions at 1:7 drug:Solutol HS 15 weight ratio showed complete and rapid drug release within 15 min at pH 1.2. The Fourier-transform infrared spectrum revealed the chemical compatibility with Solutol HS 15. Differential scanning calorimetry and X-ray powder diffraction pattern revealed a change in crystallinity to amorphous state that supported the enhancement of solubility of pioglitazone hydrochloride with Solutol HS 15. In vivo test showed that Solutol HS 15-based solid dispersions showed higher AUC 0-t and C max , which was ~4 times higher than that of pure pioglitazone (p<0.05) implying solid dispersions could be effective in increasing the bioavailability. In conclusion, solid dispersions with Solutol HS 15 prepared using solvent evaporation method appeared to be a promising technique to improve the dissolution, bioavailability and stability of pioglitazone hydrochloride.

An Albumin-Enriched Nanocomplex Achieves Systemic Delivery of Clopidogrel Bisulfate to Ameliorate Renal Ischemia Reperfusion Injury in Rats

“…The diffraction peak of HS-15 had two sharp peaks, indicating that most of HS-15 was amorphous and a small part was crystal. 51 The diffraction peak intensity of HS-CLP-NPs and BH-CLP-NPs decreased after lyophilization, but some of the diffraction peaks remained the same as that of CLP, indicating that some of the CLP crystals were retained and did not change after lyophilization. The diffraction peak intensity of BH-CLP-NPs was lower than that of HS-CLP-NPs, indicating that BSA was adsorbed onto the HS-CLP-NP surfaces.…”

Enhancement of Pioglitazone Hydrochloride Solubility Through Liquisolid Compact Formulation Using Novel Carrier Neusilin US2

“…The tube was heated and the melting of drug particles at a certain temperature was observed. The temperature was noted down when the particles just started to melt and after removing the burner noted the temperature at which the reappearance of solid structure (Flashpoint) [10].…”

Solid Dispersion as a Technical Solution to Boost the Dissolution Rate and Bioavailability of Poorly Water-Soluble Drugs

“…5,16 This feature prevents recrystallization while, enhances the dissolution rate, physical and chemical stability of the formulated drug. 22 Gelucire 44/14 and Solutol HS 15 are two examples of surfactants used to enhance the drug dissolution rate, while polymers of low glass transition temperature (T g ) such as poloxamer (P 188 ) can inhibit recrystallization. [22][23][24]…”

“…22 Gelucire 44/14 and Solutol HS 15 are two examples of surfactants used to enhance the drug dissolution rate, while polymers of low glass transition temperature (T g ) such as poloxamer (P 188 ) can inhibit recrystallization. [22][23][24]…”