Lipid based self nanoemulsifying drug delivery system (SNEDDS) was explored to improve the oral bioavailability of olanzapine (OLZ), a poorly water-soluble drug candidate, using spontaneous emulsification method. Nanoemulsions have ability to enhance the oral bioavailability of poorly water soluble or lipophilic drugs through selective lymphatic pathways. Following optimization, (from pseudo ternary phase diagram) OLZ SNEDDS consisting of Capryol 90(36.2%), Brij 97(14.6%) and ethanol (42.5%) were selected. The globule size (90 nm), and polydispersity index (0.287), was found to be minimum. The pharmacokinetic study was conducted on rabbits and the parameters like peak concentration (C max), time of peak concentration (T max), etc. were evaluated by Wagner nelson method. The in vivo studies concluded that there was 1.2 fold and 1.6 fold increase in bioavailability of nanoemulsion when compared with marketed tablet formulation and drug suspension, respectively. This may be attributed to increased solubility and enhanced permeability of the drug from nanosized emulsion. From the similarity factor between biorelevent dissolution media and 0.1 N HCl (pH 1.6) it was concluded that the 0.1 N HCl (pH 1.6) can be used for the dissolution of SNEDDS to predict the in vivo bioavailability instead of the biorelavent media. The level A correlation with correlation factor 0.97 was achieved, which showed that there is a good correlation between in vitro dissolution and in vivo bioavailability and the dissolution studies can be used as a surrogate for the in vivo studies.
A model immunosuppressant BCS Class II drug was selected for the work to assess the formulation variables on the release rate using design of experiment (DoE) - Stat-Ease software. Surface solid dispersion was prepared with dichloromethane (DCM) and ethanol mixture (4:1), and converted to tablet by adsorption on a neutral carrier. Different batches were prepared with DoE full factorial design. The concentrations of Polaxamer 188, Kollidon CL and magnesium stearate were found to be the critical factors affecting the performance of the tablets. These parameters were selected as the independent variables in DoE and the formulated batches were evaluated for their percentage release at 120 minutes. The actual and predicted plots fall close to the line. ANOVA (partial sum squares-type-III) reveals the model with F-value of 1417.12 which implies significant. The optimized batch with dissolution profile of 99.6% falls close to the innovator product 98.8%.
In this paper the author emphasizes on the basic principle of Modulated Temperature Differential Scanning Calorimetry (MTDSC), advantages of MTDSC compared to conventional DSC, calculation of heat flow components and heat capacity components, factors effecting the MTDSC signals and application of MTDSC in drug development. MTDSC a sinusoidal modulation is overlaid on a conventional linear heating ramp, in which the sample temperature increases continuously with time. The linear heating rate gives the information same as the standard DSC, while the sinusoidal heating rate determines the fraction of the total heat flow corresponding to the changing heat rate. The total heat flow rate depends on heat capacity and change in heat capacity. This fraction of heat flow is called Reversing heat flow or the heat capacity component of the Total heat flow. The kinetic component is time dependent, also known as Non-reversing heat flow that does not respond to the changing heating rate. For accurate measurements of heat flow components and heat capacity components optimized experimental parameters must be chosen. MTDSC in particularly plays an preformulation studies to establish Tg, polymorphic forms, polymorphic transitions, ensure stability by drug excipient compatability studies and to determine enthalpy of polymorphic transitions.
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