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Darunavir is effective against wild-type and PI-resistant HIV, and has an oral bioavailability of 37%. It needs to be combined with ritonavir, which increases the bioavailability to 82%. The aim of this study was to evaluate thein-vivoefficacy of the darunavir-SLN and demonstrate lymphatic transport as a contributing pathway in increasing the drug bioavailability. The SLN was prepared by hot-homogenization technique using GMS as lipid.In-vitrodrug release from SLN at the 12th hour was retarded (80.6%) compared to marketed tablet (92.6%).Ex-vivoapparent permeability of the freeze-dried SLN across everted rat intestine was 24 × 10−6at 37 °C and 5.6 × 10−6at 4 °C. The presence of endocytic process inhibitors like chlorpromazine and nystatin reduced it to 18.8 × 10−6and 20.2 × 10−6, respectively, which established involvement of endocytic mechanism in the uptake of SLN.In-vivopharmacokinetic studies on rats demonstrated increase in the AUC of SLN (26) as compared to that of marketed tablet (13.22), while the presence of lymphatic uptake inhibitor cycloheximide lowered the AUC of SLN to 17.19 which further led credence to the involvement of lymphatic uptake behind improved bioavailability. The detection of darunavir in the lymphatic fluid of the rats administered with darunavir-SLN further reinforced the conclusion of SLN being taken up by the lymphatic system. [ABSTRACT FROM AUTHOR]

Context: Lipoidal systems have particularly shown potential for specific accumulation in areas with inflamed tissue increasing the selectivity of local drug delivery. Objective: Formulation and evaluation of self-microemulsifying drug delivery system (SMEDDS) for colon-specific drug delivery for effective treatment of colonic diseases. Method: Ternary phase diagram was used to optimize level of oil, surfactant and co-surfactant to optimize SMEDDS and were evaluated for percent transmittance, emulsification time,in vitrorelease, myeloperoxidase (MPO) activity and intestinal accumulation. The spray dried SMEDDS were filled in capsules which were enteric coated with Eudragit S-100 at 10% weight gain to ensure SMEDDS delivery at colon. The spray dried SMEDDS were also evaluated for IR, DSC, XRD, SEM and stability study. Result: In ternary phase diagram, Capmul MCM C8 and Capmul PG12 NF with surfactant (Tween 20) and co-surfactant (PG) in ratio 2:1 and 3:1, respectively, showed maximum emulsification area. These liquid SMEDDS show maximum transmittance, globule size of 90–30 nm. The spray-dried SMEDDS with diluents show good flow property. The units of MPO activity show lower level as compared to pure drug and control group, histopathology results supports better healing with SMEDDS. This was attributed to accumulation of SMEDDS in inflammatory area as compared to drug which was further proved by accumulation study. Enteric-coated capsule containing SMEDDS are able to deliver drug, specifically at the colonic region. Conclusion: Higher accumulation of lipoidal drug in inflammatory area and specific release of liposomes by enteric-coated capsules provide better option for the treatment of colonic disease. [ABSTRACT FROM PUBLISHER]

The aim of the current study was to design sustained release matrix tablets of venlafaxine hydrochloride using ion exchange resin with the incorporation of hydrophilic and hydrophobic polymer combinations. Venlafaxine HCl was loaded onto Indion 244 by batch method and then resinate were wet granulated with ethyl cellulose and blended with hydroxypropylmethylcellulose and compressed. A central composite design for 2 factors at 3 levels each was employed to systematically optimize drug release profile at 2 h and at 18 h. Hydroxypropylmethylcellulose and ethylcellulose were taken as the independent variables. Response surface plots and contour plots were drawn, and optimum formulations were selected by feasibility and grid searches. Resinate shows inadequate sustained release profile. Compressed matrices exhibited the anomalous release mechanism, as the value of release rate exponent (n) varied between 08109 and 08719, resulting in regulated and complete release until 20 h. Validation of optimization study, performed using five confirmatory runs, indicated very high degree of prognostic ability of response surface methodology, with mean percentage error as 1.152±1.88%. Regulated drug release study indicates that the hydrophilic and hydrophobic matrix tablets of venlafaxine resinate prepared using hydroxypropylmethylcellulose and ethylcellulose, can successfully be employed as a once-a-day oral controlled release drug delivery system. [ABSTRACT FROM AUTHOR]

Lopinavir is a BCS Class IV drug exhibiting poor bioavailability due to P-gp efflux and limited permeation. The aim of this research was to formulate and characterize microspheres of lopinavir using thiolated xyloglucan (TH-MPs) as carrier to improve its oral bioavailability without co-administration of ritonavir. Thiomeric microspheres were prepared by ionotropic gelation between alginic acid and calcium ions. Interaction studies were performed using Fourier transform infrared spectroscopy (FT-IR). The thiomeric microspheres were characterized for its entrapment efficiency, T 80 , surface morphology, and mucoadhesion employing in vitro wash off test. The microspheres were optimized by 3 2 factorial design. The optimized thiomeric microsphere formulation revealed 93.12% entrapment efficiency, time for 80% drug release (T 80 ) of 358.1 min, and 88% mucoadhesion after 1 h. The permeation of lopinavir from microspheres was enhanced 3.15 times as determined by ex vivo study using everted chick intestine and increased relative bioavailability over 3.22-fold over combination of lopinavir and ritonavir as determined by in vivo study in rat model.