Nanosuspensions of Selexipag: Formulation, Characterization, and in vitro Evaluation

Abstract

Selexipag is an orally selective long-acting prostacyclin receptor agonist, which indicated for the treatment of pulmonary arterial hypertension. It is practically insoluble in water ( class II, according to BCS). This work aims to prepare and optimized Selexipag nanosuspensions to achieve an enhancement in the in vitro dissolution rate. The solvent antisolvent precipitation method was used for the production of nanosuspension, and the effect of formulation parameters (stabilizer type, drug: stabilizer ratio, and use of co-stabilizer) and process parameter (stirring speed) on the particle size and polydispersity index were studied. SLPNS prepared with Soluplus® as amain stabilizer (F15) showed the smallest particle size 47nm with PDI and Zeta potential value of 0.073 and -47mV, respectively. SLPNS exhibited an increase in the dissolution rate in phosphate buffer pH 6.8 (100% drug release during 60 min) compared to the pure drug ( 40% during the same time). This result indicates that SLPNS is an efficient way of improving the dissolution rate.

Preparation and In-vitro Evaluation of Darifenacin HBr as Nanoparticles Prepared as Nanosuspension

“…(SD). 7,11 Zeta Potential Evaluation of Nanosuspension Zeta-potential is evaluated using zeta sizer (Zetasizer Nano ZS, Malvern instrument, Worcestershire, UK). The zeta potential describes the extent of repulsion among neighboring and identically charged particles in the dispersion media.…”

“…The cumulative percentage release was calculated at 284 nm depending on the calibration curve. 11,14 Freeze Drying of Nanosuspension Freeze drying is used to convert the optimum formula to dry powder, later for further evaluation. Mannitol is used as a cryoprotectant at 3% w/v.…”

Ameliorating the Poor Dissolution Rate of Selexipag in Aqueous Acidic Conditions Following Confinement into Mesoporous Silica

“…This is explained by the physicochemical nature of SXP, which is a highly permeable drug with low water solubility that is categorized as a class II drug by the Biopharmaceutics Classification System. 6 The solubility profile of SXP was reported to be pH dependent, exhibiting a high solubility in alkaline media while being insoluble in acidic conditions. 6 In terms of patient convenience, effectiveness, patientfriendliness, and least invasiveness, the oral route is considered the most satisfactory, efficient, tolerant, and least invasive compared to other methods of drug administration.…”

“…6 The solubility profile of SXP was reported to be pH dependent, exhibiting a high solubility in alkaline media while being insoluble in acidic conditions. 6 In terms of patient convenience, effectiveness, patientfriendliness, and least invasiveness, the oral route is considered the most satisfactory, efficient, tolerant, and least invasive compared to other methods of drug administration. 7 In spite of these positive aspects, oral administration has several limitations, including the drug susceptibility to enzymes under different enzymatic and pH conditions of the Gastrointestinal Tract (GIT), the challenges encountered in controlling drug release, and the low dissolution, absorption, and bioavailability of several drugs from the GIT.…”

“…7 In spite of these positive aspects, oral administration has several limitations, including the drug susceptibility to enzymes under different enzymatic and pH conditions of the Gastrointestinal Tract (GIT), the challenges encountered in controlling drug release, and the low dissolution, absorption, and bioavailability of several drugs from the GIT. 8 Nanoparticle systems have gained significant interest as drug carriers because of their ability to overcome the barriers of the GIT more effectively than other formulation strategies such as nanosized solid dispersion, 9,10 nanosuspension, 6 nanoliposomes, 11 nanoemulsion, 12 and nanomicelles. 13 Nanoparticles offer several advantages, including increased drug solubility, improved bioavailability, sustained drug release, and targeted drug delivery, making them an attractive option for drug development.…”