Solid Dispersions as a Technological Strategy to Improve the Bio-Performance of Antiparasitic Drugs with Limited Solubility

Santiago N Campos,Analía I Romero,Mercedes Villegas,Alicia G Cid,Elio E Gonzo,Cintia A Briones Nieva,José M Bermúdez

doi:10.3390/iecp2020-08686

Santiago N Campos, Analía I Romero + Show 5 more

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https://doi.org/10.3390/iecp2020-08686

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Abstract

Albendazole (ABZ) and benznidazole (BZL) are drugs with low solubility used in parasitic infections treatment. In this research, solid dispersion (SD) technology was used to enhance ABZ and BZL performance by increasing their dissolution rate and solubility. SDs were prepared by the fusion method, employing Poloxamer 407 (P407) as carrier to disperse 32 of BZL or 50% w/w of ABZ. Furthermore, physical mixtures (PM) of P407 and either ABZ or BZL were also prepared, and then SDs and PMs were characterized. Dissolution tests of SDs, PMs and commercial formulations (CF) of ABZ and BZL were carried out and dissolution profiles were analyzed with the lumped mathematical model, which allowed parameters of pharmaceutical relevance to be obtained. The results indicated that ABZ SD presented an initial dissolution rate (IDR) 21-fold and 11-fold faster than PM and CF, respectively, while the IDR of BZL SD was 2.5-fold and 4.5-fold faster than PM and CF, respectively. For BZL formulations, the time required to reach 80% dissolution of the drug (t80%) was 4 (SD), 46 (PM), and 239 min (CF), while the dissolution efficiency (DE) at 30 min was 85 (DS), 71 (MF) and 65% (FC). For ABZ formulations, t80% was 2 (SD), value not reached (PM) and 40 min (CF), while the DE at 30 min was 85 (SD), 36 (MF) and 65% (CF). The SDs developed notably increased the dissolution rate, in consonance with the values obtained from the pharmaceutical parameters, which could lead to faster absorption and, consequently, increase the bioavailability of these drugs.

Highlights

While albendazole (ABZ) is an antiparasitic drug used in both human and veterinary medicine for the treatment of parasitic infections [1], benznidazole (BZL) is a first-line drug against Chagas disease [2]
Several peaks in the diffraction profiles indicated that extracted BZL (E-BZL) and P-ABZ were in crystalline state whith characteristic peaks at 7.41, 10.9, 16,9, 22, 23.7, and 25.4°, and 6.80, 11.30, 13.8, 17.9, 19.5, 20.8, 22.1, 24.43, 24.6, 27.2, 28.4 and 29.9° for E-BZL and P-ABZ, respectively
solid dispersion (SD) and physical mixtures (PM) spectra indicated that some peaks of both drugs were attenuated

Summary

Introduction

While albendazole (ABZ) is an antiparasitic drug used in both human and veterinary medicine for the treatment of parasitic infections [1], benznidazole (BZL) is a first-line drug against Chagas disease [2]. They both are classified as class II drugs by the Biopharmaceutical Classification System (BCS) due to their low solubility, limiting their bioavailability [1,2]. In 1961, Sekiguchi found that eutectic mixtures of poor soluble drugs and a inert soluble matrix enhanced drug dissolution rate and its bioavailability [16]. In 1971, Chiou and Riegelman defined the therm solid dispersion (SD) as a dispersion of one or more active ingredients in a inert matrix or carrier in solid state [17]

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