Formulation development of an albendazole self-emulsifying drug delivery system (SEDDS) with enhanced systemic exposure / Razvoj samoemulzifirajućeg sustava za isporuku albendazola (SEDDS) s pojačanom sistemskom apsorpcijom

Abstract

Most of the new chemical entities (NCEs) are poorly water-soluble and pose a challenge to developing an optimum solid oral dosage form. Oral route has been the major route of drug delivery for the treatment of various diseases. Delivery of poorly water--soluble molecules by oral route is difficult because approximately 40 % of drug compounds are limited to low aqueous solubility, which leads to restricted oral bioavailability, high intra-and inter-subject variability and lack of dose proportionality (1).To increase the oral bioavailability of poorly water-soluble compounds and eliminate the discussed drawbacks, various other formulation strategies have been adopted, including the use of cyclodextrins, nanoparticles, solid dispersions and permeation en- The aim of the study was to develop and evaluate a self--emulsifying drug delivery system (SEDDS) formulation to improve solubility and dissolution and to enhance systemic exposure of a BCS class II anthelmetic drug, albendazole (ABZ). In the present study, solubility of ABZ was determined in various oils, surfactants and co-surfactants to identify the microemulsion components. Pseudoternary phase diagrams were plotted to identify the microemulsification existence area. SEDDS formulation of ABZ was prepared using oil (Labrafac Lipopfile WL1349) and a surfactant/co-surfactant (Tween 80/PEG 400) mixture and was characterized by appropriate studies, viz., microemulsifying properties, droplet size measurement, in vitro dissolution, etc. Finally, PK of the ABZ SEDDS formulation was performed on rats in parallel with suspension formulation. It was concluded that the SEDDS formulation approach can be used to improve the dissolution and systemic exposure of poorly water-soluble drugs such as ABZ.

Novel Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Oral Delivery of Olmesartan Medoxomil: Design, Formulation, Pharmacokinetic and Bioavailability Evaluation

“…Thus, the overall stability of all SNEDDS formulae under these stress conditions was found to be acceptable. These results concur with Ashok et al, who prepared Albendazole self-emulsifying drug delivery system (SEDDS) and found that a sudden change in temperature had no effect in the entropy of the system [ 52 ].…”

Formulation Development of Albendazole-Loaded Self-Microemulsifying Chewable Tablets to Enhance Dissolution and Bioavailability

“…It is poorly soluble, with an aqueous solubility of 0.2 μg/mL at 25 °C, 1 μg/mL at pH 6.0, and a log p value of 3.5. It has weak basic properties (pK a1 = 2.68 and pK a2 = 11.83) [4,5]. Albendazole falls into the biopharmaceutical classification system (BCS) class II category with a high permeability and low solubility.…”

“…Because of its low aqueous solubility, it is poorly and erratically absorbed following oral administration. Following oral administration in rats, 20–30% is absorbed, and in humans, less than 5% is absorbed [1,2,4,6].…”

“…Upon contact with the aqueous phase of the GI tract, the digestive motility of the stomach and the intestine provide the necessary agitation for the spontaneous and fine dispersion of the SMEDDS formulations because the free energy required to form the emulsion is either low and positive or negative [12]. Although albendazole has been developed as SEDDS [4] and SMEDDS [13] to enhance the dissolution and bioavailability of drugs, liquid dosage forms are inconvenient to carry and difficult to administer as compared to solid dosage forms. In addition, solid pharmaceutical preparations are more stable than liquid preparations and their portability is convenient during the manufacturing process [14].…”

Super Aqueous Solubility of Albendazole in β-Cyclodextrin for Parenteral Application in Cancer therapy

“…Recently the molecule has been successfully tested for anticancer properties against a wide range of cancers such as ovarian, breast, prostate and a number of other cancers in both in vitro and in vivo models 4-6. However, ABZ by virtue of its molecular structure is sparingly soluble in water (0.2µg/ml) although it is highly permeable through biological membranes 7. ABZ is quite soluble in organic solvents (log P = 3.5), however the inherent toxicity found in such solvents is a disadvantage 8, 9 when preparing for intravenous (IV) or intra-peritoneal (IP) formulations.…”