Orlistat-loaded solid SNEDDS for the enhanced solubility, dissolution, and in vivo performance

Abstract

BackgroundThe present study aimed to develop orlistat-loaded solid self-nanoemulsifying drug delivery system preconcentrate (SSP) with the minimum use of lipid excipients for the enhanced solubility, in vitro dissolution, lipase inhibition, and in vivo performance.Materials and methodsIn the screening of solubilizing vehicles, Solutol HS15 and Lauroglycol 90 were selected as the surfactant and oil phase, respectively. A pseudo-ternary phase diagram composed of Solutol HS15, Lauroglycol 90, and orlistat as an anti-obesity agent and lipid component was constructed, and the SSP regions were confirmed in terms of the particle size distribution in water, melting point by differential scanning calorimetry, and crystallinity by X-ray diffraction.ResultsPhysicochemical interaction between Solutol HS15 and orlistat resulted in SSP with various melting points in the range of 26°~33°C. The representative maximum orlistat-loaded SSP (orlistat/Solutol HS15/Lauroglycol 90=55/40/5, weight ratio) showed the melting point of 32.23°C and constructed uniform nanoemulsion with the particle size of 141.7±1.1 nm dispersed in water. In the dissolution test at pH 1.2 without any detergent, the SSP reached 98.12%±0.83% until 45 minutes, whereas raw orlistat showed no significant dissolution rate. The dissolution samples containing SSP showed a lipase inhibition of 90.42%±1.58% within 45 minutes. In terms of the reduction level of fat absorption in rats, the intake group of SSP gave a significantly higher fat excretion into stool than the one observed in the raw orlistat group (P<0.05).ConclusionIn conclusion, the suggested novel SSP formulation would be an effective and promising candidate for the treatment of obesity.

Combination Therapy of Metastatic Castration-Recurrent Prostate Cancer: Hyaluronic Acid Decorated, Cabazitaxel-Prodrug and Orlistat Co-Loaded Nano-System

“…The injected volume of the sample was 10 μL, and UV detection was monitored at 195 nm for ORL. 34 For CBZ testing, the detection wavelength was 230 nm. 35 The EE and DL were calculated using the equations:…”

Development of 20(S)-Protopanaxadiol-Loaded SNEDDS Preconcentrate Using Comprehensive Phase Diagram for the Enhanced Dissolution and Oral Bioavailability

“…In previous reports, phase diagrams have been used to indicate the solubilization regions of drugs and generate SNEDDS compositions using the physical state and particle size of the mixture. [16,23]. This conventional method requires numerous tests for the physical characterization of vehicles containing various ratios of different types of oils and surfactants.…”

“…The structure of PPD comprises a tetracyclic terpene sapogenin containing hydrocarbon rings, which makes this molecule water-insoluble and fairly lipophilic (Figure 1). As a solubilization technology, the self-nanoemulsifying drug delivery system (SNEDDS) has been widely applied to enhance the aqueous solubility of highly lipophilic drugs such as PPD [15][16][17][18][19]. SNEDDS formulations are generally composed of oils, surfactants (or co-surfactants), and water, and they increase drug solubilization by forming thermodynamically stable colloidal nanoemulsions in aqueous media with a particle size range of 50-200 nm [20,21].…”

Pharmacokinetics and diuretic effect of furosemide after single intravenous, oral tablet, and newly developed oral disintegrating film administration in healthy beagle dogs

“…The rotational speed was adjusted to 50 rpm. The prepared FS-ODF containing furosemide 20 mg in a sample was placed into a dissolution vessel with a sinker [ 44 ]. At each predetermined interval, the aliquot (5 mL) of the medium was collected and filtered through a membrane filter (pore size: 0.45 μm).…”