Poloxamer-Based Biomaterial as a Pharmaceutical Strategy to Improve the Ivermectin Performance

Abstract

Background: Poloxamers are promising biomaterials for drug delivery applications due to their ability to enhance biopharmaceutical properties.

Methods: This study focused on designing solid dispersions of ivermectin using poloxamer 407 by the fusion method and evaluating how variables of synthesis affect the polymer’s behavior and the resulting biopharmaceutical properties of ivermectin. Poloxamer 407 was selected based on a solubility test of preformulation studies. Initially, eight formulations were developed using different synthesis conditions, including polymer proportion, cooling gradient, and final process temperature. These were assessed by several characterization studies. Finally, saturation solubility dissolution profiles and in vitro drug release were also evaluated.

Results: A combination of techniques confirmed the compatibility between poloxamer 407 and ivermectin in the solid dispersions. The rate of temperature in the cooling process of synthesis showed a significant impact on the polymer self-assembly, affecting their ability to entrap ivermectin. The optimized solid dispersion comprised ivermectin and poloxamer 407 in a 1:1 w/w ratio prepared by rapid cooling. This decrease in the crystallinity index and the nanometric size of particles of the solid dispersions could explain their ability to improve 1600-fold the aqueous solubility, as well as enhance the drug dissolution and in vitro drug release compared to pure ivermectin.

Conclusions: Therefore, it follows that these poloxamer-based solid dispersions are promising alternatives to improve the bioavailability of ivermectin.

Introduction

Neglected infectious diseases are a group of 14 diseases that disproportionately affect communities living in vulnerable areas, presenting themselves as an obstacle to social and economic development. However, this group of diseases can be prevented, controlled, and/or eradicated through public health measures [1]. Ivermectin (IVM) is the drug of choice to treat two types of neglected infectious diseases, Onchocerciasis and Lymphatic Filariasis [2,3]. It is an avermectin-derived semi-synthetic antiparasitic agent, consisting of an 80:20 mixture of avermectin B1a and B1b (Figure 1), which exhibits a broad spectrum of activity against ectoparasites and endoparasites [4]. Despite its wide use in both human and veterinary medicine, it belongs to class II of the biopharmaceutical classification system. In other words, this drug is characterized by good permeability, but its use is limited due to its poor aqueous solubility, which results in low oral bioavailability [5]. Various strategies have been investigated to improve the therapeutic profile of IVM [6,7].

On the other hand, advanced materials with high efficiency have attracted considerable attention for drug delivery, such as poloxamers, materials with special properties such as biocompatibility, biodegradability, and good tolerance, which have versatile applications. The U.S. Food and Drug Administration has approved several forms of poloxamer for pharmaceutical applications. This family of synthetic amphiphilic triblock copolymers (Figure 1), with a hydrophobic central block and hydrophilic lateral segments, is capable of loading water-insoluble drugs and interacting with hydrophobic surfaces and biological membranes to improve the drug availability [8,9,10]. In particular, poloxamers have been reported as suitable excipients for preparing solid dispersions (SDs) with improvements in drug wettability, solubility, and dissolution [11,12,13,14,15,16]. It can be noted that previous reports employed poloxamers as stabilizers of IVM nanocrystals, resulting in improved solubility [17,18], as well as a stabilizer of IVM-loaded lipid polymer hybrid nanoparticles, which enhance IVM solubilization and thus increase its release potential for pulmonary delivery [19]. Moreover, poloxamer 407 (P407)-based polymeric micelles incorporating IVM were investigated as an alternative to drug repositioning for the treatment of leishmaniasis [20,21].

In this study, a novel biomaterial was developed to enhance the solubility and dissolution rate of IVM. SDs are effective tools in the pharmaceutical field for enhancing drug bioavailability in both laboratory and industrial scale processes. In this investigation, the development of novel SD formulations started with the evaluation of several carriers to optimize their composition. The optimized formulations, containing P407 as the carrier, were prepared at two drug-to-polymer weight ratios of 1:1 and 1:2 by the fusion method under different cooling conditions. The resulting SDs were characterized to evaluate IVM–polymer interactions, particle size, morphology, formulation stability, and their impact on IVM solubility, dissolution, and release profile. The results demonstrated that the solubility, dissolution rate, and release of the drug were significantly enhanced by the 1:1 SDs produced through the rapid cooling of the melted sample.

Download the full article as PDF here Poloxamer-Based Biomaterial as a Pharmaceutical Strategy to Improve the Ivermectin Performance

or continue reading here

Chemicals and Reagents

IVM was supplied by Todo Droga (Córdoba, Argentina), P407 and poloxamer 188 (P188) were sourced from BASF (Ludwigshafen, Alemania), polyvinylpyrrolidone k90 (PVP-k90) was obtained from Sigma-Aldrich (Burlington, MA, USA), both polyvinylpyrrolidone k30 (PVPk-30) and sorbitol were acquired from Pura Química (Córdoba, Argentina), polyethylene glycol 8000 (PEG8000) was provided by Fluka (Seelze, Germany), and polyethylene glycol 6000 (PEG6000) was sourced from Taurus (Buenos Aires, Argentina). All reagents were of analytical grade. Methanol was obtained from Cicarelli (Buenos Aires, Argentina). Additionally, doubly distilled and deionized water was generated using a Millipore Milli-Q water purification system (Millipore, Bedford, MA, USA). HPLC-grade solvents were used, including methanol from Sintorgan (Buenos Aires, Argentina) and acetonitrile supplied by J.T. Baker.

Mezzano, B.A.; Bueno, M.S.; Fuertes, V.C.; Longhi, M.R.; Garnero, C. Poloxamer-Based Biomaterial as a Pharmaceutical Strategy to Improve the Ivermectin Performance. Pharmaceutics 2025, 17, 1101. https://doi.org/10.3390/pharmaceutics17091101

Order your sample here of Kolliphor P 188 Bio here: