The objective of this study was to develop self-emulsifying drug delivery system (SEDDS) to improve solubility and enhance the oral absorption of the poorly water-soluble drug, nevirapine. This lipid-based formulation may help to target the drug to lymphoid organs where HIV-1 virus resides mainly. The influence of the oil, surfactant and co-surfactant types on the drug solubility and their ratios on forming efficient and stable SEDDS were investigated in detail. Two SEDDS (F1 and F2) were prepared and characterized by morphological observation, droplet size and zeta potential determination, cloud point measurement and in vitro diffusion study. The influence of droplet size on the absorption from formulations with varying concentration of oil and surfactant was also evaluated from two self-emulsifying formulations. Oral bioavailability of nevirapine SEDDS was checked by using rat model. Results of diffusion rate and oral bioavailability of nevirapine SEDDS were compared with marketed suspension. The absorption of nevirapine from F1 and F2 showed 1.92 and 1.98-fold increase (p50.05) in relative bioavailability, respectively, compared with that of the suspension. There was no statistical significant difference (p50.05) between F1 and F2 in their AUC and C max . This indicated that there was apparent poor correlation between the droplet size and in vivo absorption. However, nevirapine in SEDDS showed higher ex vivo stomach and intestinal permeability and in vivo absorption than the marketed suspension, suggesting that the SEDDS may be a useful delivery system for targeting nevirapine to lymphoid organs.

A new oil-in-water microemulsion-based (ME) gel containing 1% itraconazole (ITZ) was developed for topical delivery. The solubility of ITZ in oils and surfactants was evaluated to identify potential excipients. The microemulsion existence ranges were defined through the construction of the pseudoternary phase diagrams. The optimized microemulsion was characterized for its morphology and particle size distribution. The optimized microemulsion was incorporated into polymeric gels of Lutrol F127, Xanthan gum, and Carbopol 934 for convenient application and evaluated for pH, drug content, viscosity, and spreadability. In vitro drug permeation of ME gels was determined across excised rat skins. Furthermore, in vitro antimycotic inhibitory activity of the gels was conducted using agar-cup method and Candida albicans as a test organism. The droplet size of the optimized microemulsion was found to be <100 nm. The optimized Lutrol F 127 ME gel showed pH in the range of 5.68±0.02 and spreadability of 5.75±1.396 gcm/s. The viscosity of ME gel was found to be 1805.535±542.4 mPa s. The permeation rate (flux) of ITZ from prepared ME gel was found to be 4.234 μg/cm/h. The release profile exhibited diffusion controlled mechanism of drug release from ME ITZ gel. The developed ME gels were nonirritant and there was no erythema or edema. The antifungal activity of ITZ showed the widest zone of inhibition with Lutrol F127 ME gel. These results indicate that the studied ME gel may be a promising vehicle for topical delivery of ITZ.

Elementary osmotic pumps (EOP) are well known for delivering moderately soluble drugs at a zero order rate. A push-pull osmotic system was developed and commercialized for poorly water-soluble drugs [Procardia XL (Nifedipine), Glucotrl XL (Glipizide)]. However, the technology is complex comprising of bilayer compression and the suspension of drug formed in the core has more viscosity and has to withstand the osmotic pressure within the tablet, for which the membrane must be thicker than that of EOP. The aim of the present study was to develop a solid dispersion based EOP system for a poorly water-soluble drug, nifedipine and deliver it in a zero order fashion over an extended period of time. Solid dispersions were prepared by hot melt technique using Poloxamer-188 at various ratios of drug and polymer (1:1, 1:5 and 1:10, on weight basis) and investigated for solubility study. Formation of complex and decrease in crystallinity was confirmed from differential scanning calorimetry (DSC) and X-ray crystallography (XRD) study. Core tablets using solid dispersions were prepared and coated with cellulose acetate and PEG-400. An orifice was drilled manually to create passage for drug release. The system was optimized for amount of osmogent, membrane weight gain, amount of plasticiser and diameter of the orifice, to achieve desired release profile. The osmotic system was found to deliver nifedipine at a zero order rate for 20 h. The drug release from the developed formulation was independent of pH and agitational intensity.

Poorly water-soluble drug, itraconazole (ITZ) offers a challenge in developing a drug product with adequate bioavailability. The potential for lipidic self-emulsifying drug delivery system to improve the oral bioavailability of ITZ was investigated in fasted rats. A series of ITZ SEDDS were prepared in three groups based on oil:S/CoS mixture ratios (1:9, 1:6 and 1:4) using Capryol 90 (oil), a mixture of Labrasol and Tween 20 (-surfactants) and Transcutol P (co-surfactant). The multicomponent delivery systems were optimized by evaluating their ability to self-emulsify when introduced in simulated gastric fluid, without pepsin, under gentle agitation and by determination of droplet size and visual observation. Three formulations (F5, F21 and F27), one from each group were selected based on droplet size and visual observation. The effect of oil and surfactants content on mean globule size of resulting emulsions was studied. It was clear that oil to surfactant and co-surfactant ratio has the main impact on the droplet size of the emulsion formed after dilution. However, the relation between droplet size and in vivo absorption of ITZ was futile. The order of AUC was 1:4 [ 1:6 [ 1.9 for oil:S/CoS mixture ratios. Following an oral administration of developed SEDDS and marketed capsule to rats, a 1.7, 2.0 and 2.33-fold increase in bioavailability was observed for F5, F21 and F27 respectively, compared with marketed capsule. The results from this study demonstrate the potential use of SEDDS to provide an effective way of improving oral absorption of lipophilic drugs.

Lithium carbonate, a drug with narrow therapeutic index, needs therapeutic drug monitoring and dose adjustment to maintain lithium level within the therapeutic window. Conventional formulations of lithium carbonate exhibit immediate drug release causing swing/fluctuations in the plasma concentration of lithium, consequently leading to unfavorable side-effects and make dose adjustment difficult. The push-pull osmotic pump has been developed for zero order delivery of lithium carbonate for a period of 24 h. The effect of various formulation variables on bilayer core tablet and its semi permeable coating along with orifice diameter have been investigated and optimized for desired drug release profile. Drug release was found to be inversely proportional to the membrane thickness but directly related to the amount of pore formers in the semipermeable membrane. Images from a scanning electron microscope confirmed the presence of pores in the semipermeable membrane which facilitated the required water penetration. No distortion or change in orifice shape was noticed prior to and after the dissolution study. Drug release from the developed formulation was found to be independent of pH, agitation intensity and agitation mode but depended on osmotic pressure of dissolution media.