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Fahmy, A. M., D. A. El-Setouhy, B. A. Habib, and S. A. Tayel, "Enhancement of Transdermal Delivery of Haloperidol via Spanlastic Dispersions: Entrapment Efficiency vs. Particle Size.", AAPS PharmSciTech, vol. 20, issue 3, pp. 95, 2019 Jan 29. Abstract

Haloperidol (Hal) is a well-known typical antipsychotic. Hepatic first pass metabolism leads to its limited oral bioavailability. This study aimed at enhancing transdermal delivery of Hal via spanlastic formulae. Hal-loaded spanlastics of Span®60 and an edge activator (EA) were successfully prepared by ethanol injection method according to a 3.4 full factorial design. In this design, independent variables were X, EA type, and X, Span®60 to EA ratio. Y, percentage entrapment efficiency (EE%); Y, particle size (PS); Y, deformability index (DI); and Y, percentage drug released after 4h (Q4h), were chosen as dependent variables. The Fourier-transform infrared spectral analysis showed no considerable chemical interaction between Hal and the used excipients. Both factors affected significantly all the responses except DI. Desirability of each prepared formula was calculated based on maximizing EE% and Q4h and minimizing PS. Formula F6, with X, Tween®80, and X, 8:2, had the highest desirability value followed by F7, with X, Tween®80, and X, 6:4, and both were chosen as selected formulae (SF) for further investigation. F6 (having more entrapped Hal), F7 (of smaller PS), and Hal solution in propylene glycol were subjected to ex vivo permeation test through newborn rat skin. Both formulae showed marked enhancement in drug permeation compared with drug solution. The significantly higher Q and J of F7 from F6 may indicate that the smaller particle size aided more than higher entrapment in achieving a higher permeation for Hal of 3.5±0.2μg/cm.h. These results are promising for further investigation of this formula.

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