monooctanoin and carbitol

A novel, supersaturable self-microemulsifying drug delivery system (S-SMEDDS) was successfully formulated to enhance the dissolution and oral absorption of valsartan (VST), a poorly water-soluble drug, while reducing the total quantity for administration. Poloxamer 407 is a selectable, supersaturating agent for VST-containing SMEDDS composed of 10% Capmul

Topics: Administration, Oral; Animals; Biological Availability; Caprylates; Drug Delivery Systems; Emulsions; Ethylene Glycols; Glycerides; Male; Polymers; Polysorbates; Rats, Sprague-Dawley; Solubility; Valsartan

The current study was aimed to investigate the potential of solid self-nanoemulsifying drug delivery system (S-SNEDDS) composed of Capmul MCM C8 (oil), Tween 80 (surfactant) and Transcutol P (co-surfactant) in improving the dissolution and oral bioavailability of darunavir. Liquid self-nanoemulsifying drug delivery systems (L-SNEDDS) were developed by using rational blends of components with good solubilizing ability for darunavir which were selected based on solubility studies, further ternary phase diagram was constructed to determine the self-emulsifying region. The prepared L-SNEDDS formulations were evaluated to determine the effect of composition on physicochemical parameters like rate of emulsification, clarity, phase separation, thermodynamic stability, cloud point temperature, globule size and zeta potential. In vitro drug release studies showed initial rapid release of about 13.3 ± 1.4% within 30 min from L-SNEDDS followed by slow continuous release of entrapped drug and reached a maximum of 62.6 ± 3.5% release at the end of 24h. The globule size analysis revealed the formation of nanoemulsion (144 ± 2.3 nm) from the optimized L-SNEDDS formulation and was physically adsorbed onto neusilin US2. In vitro dissolution studies indicated faster dissolution of darunavir from the developed S-SNEDDS with 3 times greater mean dissolution rate (MDR) compared to pure darunavir. Solid state studies concluded the presence of drug in non-crystalline amorphous state without any significant interaction of drug with the components of S-SNEDDS. Furthermore, in vivo pharmacokinetic studies in Wistar rats resulted in enhanced values of peak drug concentration (Cmax) for L-SNEDDS (2.98 ± 0.19 μg/mL) and S-SNEDDS (3.7 ± 0.28 μg/mL) compared to pure darunavir (1.57 ± 0.17 μg/mL).

Topics: Administration, Oral; Animals; Biological Availability; Caprylates; Darunavir; Delayed-Action Preparations; Drug Delivery Systems; Drug Liberation; Drug Stability; Emulsions; Ethylene Glycols; Excipients; Glycerides; Half-Life; HIV Protease Inhibitors; Male; Nanostructures; Particle Size; Polysorbates; Random Allocation; Rats, Wistar; Surface Properties; Surface-Active Agents

Hydroxypropyl methylcellulose (HPMC) propels self-emulsifying drug delivery systems (SEDDS) to achieve the supersaturated state in gastrointestinal tract, which possesses important significance to enhance oral absorption for poorly water-soluble drugs. This study investigated capacities and mechanisms of HPMC with different viscosities (K4M, K15M and K100M) to inhibit drug precipitation of SEDDS in the simulated gastrointestinal tract environment in vitro. The results showed that HPMC inhibited drug precipitation during the dispersion of SEDDS under gastric conditions by inhibiting the formation of crystal nucleus and the growth of crystals. HPMC had evident effects on the rate of SEDDS lipolysis and benefited the distribution of drug molecules across into the aqueous phase and the decrease of drug sediment. The mechanisms were related to the formed network of HPMC and its viscosities and molecular weight. These results offered a reference for selecting appropriate type of HPMC as the precipitation inhibitor of supersaturatable SEDDS.

Topics: Caprylates; Chemical Precipitation; Crystallization; Drug Delivery Systems; Emulsifying Agents; Emulsions; Ethylene Glycols; Glycerides; Hypromellose Derivatives; Indomethacin; Lipolysis; Molecular Weight; Polyethylene Glycols; Viscosity

Carvedilol, a widely prescribed cardiovascular drug for hypertension and congestive heart failure, exhibits low and variable bioavailability owing to poor absorption and extensive hepatic first-pass metabolism. The current research work, therefore, entails formulation development of liquid self-nano-emulsifying drug delivery systems (SNEDDS) to enhance the bioavailability of carvedilol by facilitating its transport via lymphatic circulation. The formulation constituents, i.e. lipids, surfactants, and co-surfactants, were selected on the basis of solubility studies. Pseudo-ternary phase diagrams were constructed to embark upon the selection of blend of lipidic (i.e. Capmul PG8) and hydrophilic components (i.e. Cremophor EL as surfactant and Transcutol HP as co-surfactant) for efficient and robust formulation of SNEDDS. The SNEDDS, systematically optimized employing a central composite design (CCD), were evaluated for various response variables viz drug release parameters, emulsification time, emulsion droplet size, and mean dissolution time. In vitro drug release studies depicted that the release from SNEDDS systems followed a non-Fickian kinetic behavior. The TEM imaging of the optimized formulation affirmed the uniform shape and nano size of the system. Accelerated studies of the optimized formulation indicated high stability of the formulation for 6 months. The in situ perfusion studies carried out in wistar rats construed several fold augmentation in the permeability and absorption potential of the optimized formulation vis-à-vis marketed formulation. Thus, the present studies ratified the potential of SNEDDS in augmenting the oral bioavailability of BCS class II drugs.

Topics: Animals; Biological Availability; Caprylates; Carbazoles; Cardiovascular Agents; Carvedilol; Chemistry, Pharmaceutical; Drug Delivery Systems; Drug Stability; Emulsions; Ethylene Glycols; Excipients; Glycerides; Glycerol; Intestinal Absorption; Jejunum; Male; Microscopy, Electron, Transmission; Nanostructures; Oils; Particle Size; Perfusion; Propanolamines; Rats; Rats, Wistar; Solubility