Development of β-cyclodextrin-based hydrogel microparticles for solubility enhancement of rosuvastatin: an in vitro and in vivo evaluation

Abstract

The aim of this study was to enhance the solubility of rosuvastatin (RST) calcium by developing β-cyclodextrin-g-poly(2-acrylamido-2-methylpropane sulfonic acid [AMPS]) hydrogel microparticles through aqueous free-radical polymerization technique. Prepared hydrogel microparticles were characterized for percent entrapment efficiency, solubility studies, Fourier transform infrared spectroscopy, differential scanning calorimetry, thermal gravimetric analysis, powder X-ray diffraction, scanning electron microscopy, zeta size and potential, swelling and release studies. Formulations (HS1–HS9) have shown entrapment efficiency between 83.50%±0.30% and 88.50%±0.25%, and optimum release was offered by formulation HS7 at both pH levels, ie, 1.2 (89%) and 7.4 (92%). The majority of microparticles had a particle size of less than 500 µm and zeta potential of −37 mV. Similarly, optimum solubility, ie, 10.66-fold, was determined at pH 6.8 as compared to pure RST calcium, ie, 7.30-fold. In vivo studies on fabricated hydrogel microparticulate system in comparison to pure drug were carried out, and better results regarding pharmacokinetic parameters were seen in the case of hydrogel microparticles. A potential approach for solubility enhancement of RST calcium and other hydrophobic moieties was successfully developed.

Directly compressed rosuvastatin calcium tablets that offer hydrotropic and micellar solubilization for improved dissolution rate and extent of drug release

“…As with many poorly soluble drugs, complexation with cyclodextrin has been pursued to provide a drug containing-complex within an aqueous medium that can hold the rosuvastatin in the core, readily available for release into the physiological fluid as free drug is absorbed (Kuhad, 2017, Venkatesh et al, 2014). Polymerization of cyclodextrins with other polymers or monomers can enhance their ability to improve the dissolution rate and oral bioavailability (Sarfraz et al, 2017). β-cyclodextrin-g-AMPS hydrogel particles were prepared by a polymeric graft onto β-cyclodextrin through aqueous free radical polymerization with ammonium persulfate as the initiator and N,N′-methylene bisacrylamide as the crosslinking agent (Sarfraz et al, 2017).…”

“…Polymerization of cyclodextrins with other polymers or monomers can enhance their ability to improve the dissolution rate and oral bioavailability (Sarfraz et al, 2017). β-cyclodextrin-g-AMPS hydrogel particles were prepared by a polymeric graft onto β-cyclodextrin through aqueous free radical polymerization with ammonium persulfate as the initiator and N,N′-methylene bisacrylamide as the crosslinking agent (Sarfraz et al, 2017). pH-independent swelling of these rosuvastatin calcium-containing hydrogels is offered by the presence of 2-acrylamido-2-methylpropane sulfonic acid (AMPS) grafted onto the cyclodextrin.…”

Rosuvastatin cocrystals: an attempt to modulate physicochemical parameters

“…Cocrystals are cognominated among the products that are obtained from the crystal engineering approach with ionic/non-covalent intermolecular interaction between two or more disparate molecules with a certain stoichiometric ratio in a crystal lattice [48,49] at most one molecule should be active moiety. Generally, the choice of co-former should be done from GRAS (Generally recognized as safe) or EAFUS (Everything added to food in united states) list, which is frequently without pharmacological efficacy [50,51].…”

“…The major trouble with this drug is low water solubility (0.33 mg/ml) which displays low solubility in gastrointestinal fluids [23]. Previously, various efforts to enhance the solubility of rosuvastatin such as polymerization [24], liquisolid technology [25], and nanoemulsifying delivery systems [26] were ample in the literature. Cocrystals of rosuvastatin were formulated by utilizing sorbitol [27] and vanillin [28] as co-formers.…”

Characterization of Thermal Fraction of Clarified Butter and its Applicability to Improve Bioavailability of Rosuvastatin

“…Rosuvastatin works by reducing the total number of VLDL and LDL particles. 4 Moreover, its low bioavailability about 20% owes to its extensive extraction in the liver. Rosuvastatin is slightly soluble in water (7.8 mg/mL at 37°C) and has a pKa of 4.6.…”