Albendazole Microcrystal Formulations Based on Chitosan and Cellulose Derivatives: Physicochemical Characterization and In Vitro Parasiticidal Activity in Trichinella spiralis Adult Worms

Abstract

The oral route has notable advantages to administering dosage forms. One of the most important questions to solve is the poor solubility of most drugs which produces low bioavailability and delivery problems, a major challenge for the pharmaceutical industry. Albendazole is a benzimidazole carbamate extensively used in oral chemotherapy against intestinal parasites, due to its extended spectrum activity and low cost. Nevertheless, the main disadvantage is the poor bioavailability due to its very low solubility in water. The main objective of this study was to prepare microcrystal formulations by the bottom-up technology to increase albendazole dissolution rate, in order to enhance its antiparasitic activity. Thus, 20 novel microstructures based on chitosan, cellulose derivatives, and poloxamer as a surfactant were produced and characterized by their physicochemical properties and in vitro biological activity. To determine the significance of type and concentration of polymer, and presence or absence of surfactant in the crystals, the variables area under the curve, albendazole microcrystal solubility, and drug released (%) at 30 min were analyzed with a three-way ANOVA. This analysis indicated that the microcrystals made with hydroxyethylcellulose or chitosan appear to be the best options to optimize oral absorption of the active pharmaceutical ingredient. The in vitro evaluation of anthelmintic activity on adult forms of Trichinella spiralis identified system S10A as the most effective, of choice for testing therapeutic efficacy in vivo.

Repositioning of Anti-parasitic Drugs in Cyclodextrin Inclusion Complexes for Treatment of Triple-Negative Breast Cancer

“…The pharmacological activities of these drugs are focused in the inhibition of tubulin polymerization and blockage of glucose uptake. Thus, these compounds produce depletion of glycogen stores and decrease the adenosine triphosphate (ATP) formation in the larval and adult stages of parasites [19][20][21]. Microtubule formation is involved in cell division; therefore, its inhibition is currently one of the goals of medicinal chemistry in cancer chemotherapy [22].…”

“…Despite their therapeutic efficacy, both ABZ and RBZ present poor aqueous solubility and limited absorption after oral administration. Pharmaceutical technology has developed several strategies to overcome solubility and absorption limitations of insoluble drugs such as solid dispersions [29], micellar formulations [30,31], nano-and microstructured systems [20,32,33], co-crystals [34], and cyclodextrin (CD) inclusion complexes [35][36][37][38][39].…”

Neusilin based liquisolid compacts of albendazole: Design, development, characterization and in vitro anthelmintic activity

“…Literature reports inclusion complex and nanoclusters of cyclodextrin, albendazoledesmotropes by supramolecularsystems with maltodextrin and glutamic acid, spray drying with lactose and other water soluble excipients, microcrystals using gum karaya and hupu gum as stabilizing agents and microcrystals with chitosan and cellulose derivatives are reported for enhancement of solubility, dissolution rate and indirectly bioavailability of albendazole [8][9][10][11][12][13][14] The low cost and broad spectrum of activity of ABZ make it typically the drug of choice for these cases. However, it's very low solubility results in low absorption through the gastrointestinal tract and in some applications, such as for the systemic diseases, high oral doses that cause adverse gastrointestinal disturbances and several detrimental side effects occur [15].…”

Synthesis and characterization of a new cyclodextrin derivative with improved properties to design oral dosage forms

“…Since CDs can form water-soluble inclusion complexes with many poorly soluble lipophilic drugs, they are used to enhance the drug aqueous solubility and to improve its bioavailability after oral administration [12,13]. The formation of complexes with CDs is one of the several strategies employed to increase solubility, dissolution rate and oral bioavailability of such poorly water-soluble drugs [9,11,14,15].…”