Enhancement of the aqueous solubility and permeability of a poorly water soluble drug ritonavir via lyophilized milk-based solid dispersions

Abstract

In the present study, a lyophilized milk-based solid dispersion (SD) of ritonavir (RTV) was developed with the goal of improving its aqueous solubility. The SD was prepared by lyophilization, and characterized for its physicochemical and functional properties. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), photomicroscopy and powder X-ray diffraction (PXRD) were used to confirm the formation and robustness of the SD formulation. The prepared SD formulations were functionally evaluated by saturation solubility, in vitro drug release and ex vivo permeation studies. The optimized SD formulation exhibited a significantly higher (30-fold) aqueous solubility (11.36 ± 0.06 μg/mL), compared to the pure RTV (0.37 ± 0.03 μg/mL). The in vitro dissolution studies revealed a significantly higher (∼10-fold) efficiency of the optimized SD formulation in releasing the RTV, compared to the pure RTV. The ex vivo permeation studies with the everted intestine method showed that prepared SD formulation significantly improved the permeation of RTV (75.6 ± 3.09, % w/w), compared to pure RTV (20.45 ± 1.68, % w/w). Thus, SD formulation utilizing lyophilized milk as a carrier appears to be a promising alternative strategy to improve the aqueous solubility of poorly water soluble drugs.

Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential

“…The zeta potential value (-22.35 ± 0.30 mV) obtained for APLC was greater than -30 mV, which indicates excellent stability of the APLC from flocculation when seen in the context of its low particle size. The zeta potential with range (-20 to 30 mV) was earlier demonstrated as a characteristic property of zeta potential for attraction followed by flocculation exceeding repulsion forces (Dhore et al, 2016;Freitas and Müller, 1998). The zeta potential value depends on the type and composition of phospholipids.…”

The impact of digestion is essential to the understanding of milk as a drug delivery system for poorly water soluble drugs

“…Tris-maleate buffer (50 mM, pH 6.5) was used for the digestions and was prepared by dissolving 11.86 g of Trizma-maleate, 0.74 g of calcium chloride dihydrate (5 mM), and 8.77 g of sodium chloride (150 mM) in water to a total volume of 1000 mL. Calcium chloride was added to remove the free fatty acids from the lipolysis medium that could inhibit lipolysis and to more closely resemble in vivo conditions where the free fatty acids are absorbed [3]. The pH stat component of the lipolysis model provides an indication of the kinetics of the lipolysis reaction by monitoring the addition of sodium hydroxide in response to production of the fatty acids to maintain a constant pH (6.5 in these studies).…”

“…The fat content in mammalian milk comprises over 95% triglycerides [1]. The recognition that these milk lipids can offer a solubilising environment for poorly water-soluble lipophilic drugs has led to a range of studies focusing on the solubility of drugs in milk [[2], [3], [4], [5], [6]] and in a limited number of studies the effect of milk on in vivo absorption and bioavailability [[7], [8], [9]]. The solubility of drugs in milk has been reported to be enhanced compared to that in aqueous media without fat present and in limited in vivo studies consequent increases in systemic exposure have been demonstrated.…”

Antiviral Drug Delivery System for Enhanced Bioactivity, Better Metabolism and Pharmacokinetic Characteristics

“…A lyophilized milk-based solid dispersion was developed to enhance the solubility and permeability of ritonavir. 31 Ritonavir was dispersed in an amorphous polymer matrix and existed primarily in a molecularly dispersed state. 32 This formulation (drug:carrier mass ratio of 1:4) exhibited higher dissolution efficiency (~55.26 ± 1.29%, representing a 10-fold increase compared to pure ritonavir).…”