Formulation and Evaluation of Solid Self Nano Emulsifying drug delivery System of Olanzapine to Enhance Aqueous Solubility and Dissolution Rate

Present research work was aimed to enhance aqueous solubility and dissolution rate of olanzapine by solid self nano emulsifying drug delivery system(S-SNEDDS). Olanzapine is a BCS class II drug having 65% oral bioavailability; it is used in the treatment of psychosis, depression and mania conditions. Oils, Surfactants, Co surfactants were selected depending upon the saturated solubility of olanzapine in those components; excipients were screened depending on olanzapine solubility in various oils, surfactants and co surfactants. Surfactant: co surfactant {Smix} ratios i.e., 3:1 and 4:1 were prepared to determine nano emulsion regions and also to formulate liquid self nano emulsifying drug delivery system (L-SNEDDS). Pseudo ternary phase diagram were plotted by using Triplot version 4.1.2 software, nano emulsion region was determined and evaluated. Formulations were designed based on saturated solubility of olanzapine and Pseudo ternary phase diagram using various ratios of oils [Capryol 90], surfactants [Kolliphor EL], co surfactants [Lauroglycol 90] depending on its solubility and nano emulsion formation four formulations were developed which are further selected for characterisation of L-SNEDDS like robustness to dilution, self emulsification, determination of droplet size, PDI, Drug loading efficacy, zeta potential and also Invitro drug release. Among those four formulations, F1 (SB184J 4:6) was optimum because compared to other three formulations F3 gave best results in terms of droplet size (66nm) with PDI (0.24), Invitro drug release, dissolution rate of F1 SNEDDS having (88.201± 0.25%). Invitro drug release of F1 formulation was compared with that of Olanzapine [API] (45.281± 0.52%) the results indicating that there is a increase in solubility and dissolution rate of olanzapine by 2.2 times more compared to pure olanzapine (API). F1 (SB184J 4:6) were converted into S-SNEDDS by adsorption process by addition porous carriers (Aerosil 200). Formulated S-SNEDDS were undergone various evaluation parameters and also reconstitution parameters to determine Droplet size and Invitro drug release of solid F1 (SB184J4:6) formulation. The results of present study demonstrates that olanzapine SNEDDS has an ability and potential to enhance solubility and dissolution rate.

Amalgamation of Solid Dispersion and Melt Adsorption Techniques For Augmentation of Oral Bioavailability of Novel Anticoagulant Rivaroxaban

The objective of the present study was to evaluate the potential of solid dispersion adsorbate to improve the solubility and bioavailability of rivaroxaban (RXN). Solid dispersion adsorbate (SDA) of RXN was developed by fusion method using PEG 4000 as carrier and Neusilin as adsorbent. A 32 full factorial design was utilized to formulate various SDAs. The selected independent variables were amount of carrier (X1) and amount of adsorbate (X2). The responses measured were time required for 85% drug release (Y1) and saturated solubility (Y2). MTT assay was employed for cytotoxicity studies on Caco-2 cells. In vivo pharmacokinetics and pharmacodynamic evaluations were carried out to assess the prepared SDA. Pre-compression evaluation of SDA suggests the prepared batches (B1-B9) possess adequate flow properties and could be used for compression of tablets. Differential scanning calorimetry and X-ray diffraction data signified the conversion of crystalline form of drug to amorphous form, a key parameter accountable for improvement in drug dissolution. Optimization data suggests that the amount of carrier and amount of adsorbate significantly (P < 0.05) influence both dependent variables (time required for 85% drug release and saturated solubility). Post-compression data signifies that the compressibility behavior of prepared tablets were within the official standard limits. Significant increase (P < 0.0001) in the in vitro dissolution characteristics of RXN was noticed in optimized SDA (>85% in 10 min) as compared to pure drug, marketed product and directly compressible tablet. Cytotoxicity studies confirm nontoxicity of prepared RXN SDA tablets. Higher Cmax and AUC achieved with RXN SDA tablets indicated enhancement in oral bioavailability (~3 folds higher than the RXN suspension). Higher bleeding time and percentage of platelet aggregation noticed with RXN SDA tablets further substantiate the efficacy of the prepared formulation. In summary, the results showed the potential of RXN SDA tablets to enhance the bioavailability of RXN and hence can be an alternate approach of solid dosage form for its development for commercial application.

FORMULATION AND EVALUATION OF ATORVASTATIN CALCIUM NANOCRYSTALS CONTAINING P-GLYCOPROTEIN INHIBITORS FOR ENHANCING ORAL DELIVERY

Objective: The main objective of this study was to develop atorvastatin calcium (ATR) as an oral drug delivery system for a P-glycoprotein (P-gp) substrate drug using different pharmaceutical excipients that inhibit P-glycoprotein and evaluate the influence of nanocrystals on the dissolution characteristics and bioavailability compared to the plain drug. Methods: A nanosuspension was prepared by Solvent-antisolvent precipitation method using a solvent containing stabilizer that act as a p-gp inhibitor dissolved in distilled water as polyethylene glycol 300, polyethylene glycol 400 (PEG 300, PEG 400), tween 20 and tween 80 while the solvent selected for atorvastatin calcium was methanol. The concentrations were as follows: PEG 300 and 400 = 0.25% w/v, tween 20 and 80 = 0.75% v/v. Nanocrystals were extracted from the suspension and characterized. Results: Particle size of the drug was 1307±127.79 nm while the formulas prepared ranged from 223±17.67 to 887±58.12 nm. Pure ATR had a saturated solubility of 0.059±0.005 mg/ml and the prepared nanocrystals ranged from 0.32±0.021 to 0.88±0.019 mg/ml. The Percentage of drug released of plain atorvastatin calcium reached 41.49% while the formula ranged from 44.32 to 61.5%. Both XRD and SEM discussed the degree of crystallinity as follows: F1<F2<F4<F3<ATR. Conclusion: 0.3% of PEG 300 and PEG 400 were not enough to formulate proper nanocrystals while 0.75% tween 20 and tween 80 achieved acceptable formulas. F4 which is prepared with tween 80 exhibited the highest enhancement in saturated solubility, dissolution rate and subsequently expected to have improved oral bioavailability.

Enhancement Solubilization of Dutasteride using Microsponge Formulation

Dutasteride (DU) (5α-reductase inhibitor) that is used for the treatment of benign prostate hyperplasia (BPH), DU has low water solubility and poor oral absorption that classified as Biopharmaceutics Classification System (BCS) class II. This study aims to improve the physical properties of Dutasteride (DU) like solubility by the preparation of microsponge (MS). Microsponges are spherical in shape, sponge-like structure, polymeric delivery systems composed of porous microspheres with a large internal surface area. Nine formulations of DU MS had been prepared by the technique of quasi-emulsion solvent diffusion (QESD) and utilizing Eudragit S100 as major polymer and glycerol as a plasticizer that dissolved in dichloromethane where polyvinyl alcohol PVA serves as a stabilizer in the external phase. The formulas were employed to optimize preparation variable factors include; different drug to polymer ratio, the addition of different concentrations of PVA, and stirring rate. Optimization was done using the response of production yield (PY), entrapment efficiency EE), particle size, and in vitro drug release; The results display that the best ratio of (drug: polymer) was 5:1, and the best rate of stirring was 1,000 rpm respecting the optimum characteristics of microsponge. The best-selected formula prepared (F2) was underwent to evaluation regarding saturated solubility, FTIR, DSC, and SEM and showed 1.28 folds enhancement in saturated solubility compared to plain DU, and was well fabricated with high entrapment efficiency (83.7% ± 1.37), production yield (85.61% ± 0.6), and particle size of 77μm. Moreover, the percent release of DU was 75.74 ± 1.5 after 4 hours, with good compatibility as confirmed by XRD, SEM, DSC, and fourier-transform infrared spectroscopy (FTIR) analysis. It can be concluded that the selected formula prepared (F2) of DU microsponge is reassuring and promising drug delivery with improved pharmaceutical physical properties.