Enhancement of the aqueous solubility and permeability of a poorly water soluble drug ritonavir via lyophilized milk-based solid dispersions.
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.
a Department of Pharmaceutical Sciences , R.T.M. Nagpur University , Nagpur , India.
Pradip W
PW
Dhore
b Wegmans School of Pharmacy, St. John Fisher College , Rochester , NY , USA.
Vivek S
VS
Dave
a Department of Pharmaceutical Sciences , R.T.M. Nagpur University , Nagpur , India.
Suprit D
SD
Saoji
a Department of Pharmaceutical Sciences , R.T.M. Nagpur University , Nagpur , India.
Yamini S
YS
Bobde
b Wegmans School of Pharmacy, St. John Fisher College , Rochester , NY , USA.
Connor
C
Mack
a Department of Pharmaceutical Sciences , R.T.M. Nagpur University , Nagpur , India.
Nishikant A
NA
Raut
D000818:Animals; D002152:Calorimetry, Differential Scanning; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D005612:Freeze Drying / Q000379:methods; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008823:Micelles; D008892:Milk / Q000737:chemistry; D010539:Permeability; D033362:Powder Diffraction; D017207:Rats, Sprague-Dawley; D019438:Ritonavir / Q000737:chemistry* / Q000493:pharmacokinetics*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
D065692:Cytochrome P-450 CYP3A Inhibitors; D017320:HIV Protease Inhibitors; D008823:Micelles; D014867:Water; D019438:Ritonavir
Complexation; dissolution; milk micelle; permeability; solubility