Formulation of Rosuvastatin-Loaded Self-Nanoemulsifying Drug Delivery System Using Box-Behnken Design

Ahsan, Mohd Neyaz; Verma, Priya Ranjan Prasad; Singh, Sandeep Kumar; Samridhi,; Yashpal, Madhu

doi:10.1080/02726351.2013.800929

Cited by 13 publications

(11 citation statements)

References 33 publications

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“…This might be as a consequence of cosurfactant ability to lower the interfacial tension by penetrating the surfactant film, fluidizing the hydrocarbon region of the interfacial film which induces formation of void spaces between the surfactant molecules. This help in emulsification process and thus lowers the emulsification time [54].…”

Section: Discussionmentioning

confidence: 99%

Application of Box–Behnken design and desirability function in the development and optimization of self-nanoemulsifying drug delivery system for enhanced dissolution of ezetimibe

2020

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Background: This study is focused on developing and optimizing a self-nanoemulsifying drug delivery system (SNEDDS) of BCS class II drug (ezetimibe) through Box-Behnken design (BBD) and desirability function for enhanced dissolution. Pseudoternary phase diagrams were created by taking oil (Peceol), surfactant (Tween80), and co-surfactant (Transcutol-P) and the concentration ranges were identified for generating BBD. The composition of ezetimibe-SNEDDS was optimized through various response variables viz. globule size (Y 1), %transmittance (Y 2), selfemulsification time (Y 3), dissolution after 5 min and 40 min (Y 4 , Y 5). Optimized formulation was characterized for various physicochemical properties. Results: Pseudoternary phase diagram having maximum nano-emulsification area was selected to formulate SNEDDS. Derived polynomial equation and model graphs were exercised to investigate the impact of formulation variables on the responses. Significant effect of formulation composition on the responses was observed (p < 0.05). The formulation with least oil (10%) and high surfactant (60%) exhibited low globule size (24.4 ± 2.07 nm), low emulsification time (55 s) but high %transmittance (101.2%) and drug release (49.21% after 5 min; 95.27% after 40 min). Based on the desirability function, the optimized formulation was selected and reformulated. The optimized formulation (FF1) was found to be uniform, stable, and showed similar observed and predicted responses. Conclusion: The potential of SNEDDS in improving the dissolution profile of weakly soluble drug and the applicability of BBD with desirability function in optimizing a SNEDD formulation has made it possible to identify the impact of various independent variables on optimization of the formulation for better responses.

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Section: Discussionmentioning

confidence: 99%

Application of Box–Behnken design and desirability function in the development and optimization of self-nanoemulsifying drug delivery system for enhanced dissolution of ezetimibe

2020

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“…The absorbances of aqueous dispersion (100 mL) of F1-F9 formulations (100 mg) were obtained spectrophotometrically at 400 nm (UV-Vis Spectrophotometer, 1800, Shimadzu, Japan) at 2 and 24 h, in order to categorize the formulations based on their visual clarity and also to study their precipitation behavior 24 h post-dispersion 30 . The correlation between the absorbance and mean globule size was later determined.…”

Section: Evaluation and Characterizationmentioning

confidence: 99%

Fabrication of lipidic nanocarriers of loratadine for facilitated intestinal permeation using multivariate design approach

Verma

Singh

Verma

2015

Drug Development and Industrial Pharmacy

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In this investigation, multivariate design approach was employed to develop self-nanoemulsifying drug delivery system (SNEDDS) of loratadine and to exploit its potential for intestinal permeability. Drug solubility was determined in various vehicles and existence of self-nanoemulsifying region was evaluated by phase diagram studies. The influence of formulation variables X1 (Capmul MCM C8) and X2 (Solutol HS15) on SNEDDS was assessed for mean globule sizes in different media (Y1-Y3), emulsification time (Y4) and drug-release parameters (Y5-Y6), to improve quality attributes of SNEDDS. Significant models were generated, statistically analyzed by analysis of variance and validated using the residual and leverage plots. The interaction, contour and response plots explicitly demonstrated the influence of one factor on the other and displayed trend of factor-effect on responses. The pH-independent optimized formulation was obtained with appreciable global desirability (0.9266). The strenuous act of determining emulsification time is innovatively replaced by the use of oil-soluble dye to produce visibly distinct globules that otherwise may be deceiving. TEM images displayed non-aggregated state of spherical globules (size < 25 nm) and also revealed the structural transitions occurring during emulsification. Optimized formulation exhibited non-Newtonian flow justified by the model-fit and also presented the stability to dilution effects and thermodynamic stress testing. The ex vivo permeation study using confocal laser scanning microscopy indicate strong potential of rhodamine 123-loaded loratadine-SNEDDS to inhibit P-gp efflux and facilitate intestinal permeation. To conclude, the effectiveness of design yields a stable optimized SNEDDS with enhanced permeation potential, which is expected to improve oral bioavailability of loratadine.

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“…1 , 2 RST is a lipophilic (log P = 2.4) candidate with low water solubility (0.33 mg/mL), poor in vivo dissolution in physiological fluids, and limited oral absorption resulting in least oral bioavailability (∼20%). 3 …”

Section: Introductionmentioning

confidence: 99%

“…Maximum solubility values of RST in propylene glycol (PG) and (polyethylene glycol 400) PEG400 were reported as 1.89 × 10 –2 (mole fraction solubility at 318.15 K) and 65.7 mg/g, respectively. 3 , 4 Several authors used ethanol, PEG200, and PEG400 as cosolvents with water to form new mixture ratios to improve lipophilic drug solubility in the explored temperature range. 5 − 7 The concept of cosolvency technique has widely been used for formulation development, water treatment from wastewater treatment plant, and purification studies.…”

Section: Introductionmentioning

confidence: 99%

“…The reported oral dose of RST is approximately in the range of 5–40 mg daily for adults. 3 The dose can also be delivered using the biocompatible {PEG400 (1) + water (2)} cosolvent mixture for the alternative route (such as subcutaneous) of drug administration to the oral dosage form. Hence, the present study examined the solubilization of RST in the aqueous solution of PEG400 at 25.0 °C and varied ratios of PEG400 in water.…”

Section: Introductionmentioning

confidence: 99%

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Preferential Solvation Study of Rosuvastatin in the {PEG400 (1) + Water (2)} Cosolvent Mixture and GastroPlus Software-Based In Vivo Predictions

et al. 2023

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Rosuvastatin (RST) is a poorly water-soluble drug responsible for limited in vivo dissolution and subsequently low oral systemic absorption (poor bioavailability). The mole fraction solubility values of RST in various ratios of binary mixtures “{PEG400 (1) + water (2)}” at 298.15 K were employed to investigate the preferential solvation (PS) of RST (3) by the binary components. Moreover, the GastroPlus program predicted the drug dissolution/absorption rates, plasma drug concentration, and compartmental regional drug absorbed from a conventional tablet as compared to the RST-loaded (PEG400 + water) mixture (at x 1 = 0.5) in healthy subjects (considering the fast condition). Fedors’ method was adopted to estimate the values of molar volume (314.8 cm3·mol–1) and Hildebrand solubility parameter (28.08 MPa1/2) of RST. The results of inverse Kirkwood–Buff integrals showed the PS of RST by PEG400 as observed in all studied ratios of the binary mixture. The highest PS value (δx 1,3 = 1.65 × 10–2) for RST by PEG400 was attained at x 1 = 0.5. Finally, the GastroPlus program predicted the maximum dissolution rate [20 mg within 15 min as compared to pure RST (1.5 mg within 15 min)]. Moreover, the program predicted increased in vivo oral absorption (1.2 μg/mL) and enhanced regional absorption (95.3%) of RST from upper segments of the gastrointestinal tract for the RST-loaded PEG400 + water mixture in humans as compared to conventional tablets (87.5% as total regional absorption and 0.88 μg/mL as in vivo absorption). Hence, the present binary system ferrying RST can be a promising strategy to control systemic dyslipidemia after oral or subcutaneous administration.

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Formulation of Rosuvastatin-Loaded Self-Nanoemulsifying Drug Delivery System Using Box-Behnken Design

Cited by 13 publications

References 33 publications

Application of Box–Behnken design and desirability function in the development and optimization of self-nanoemulsifying drug delivery system for enhanced dissolution of ezetimibe

Application of Box–Behnken design and desirability function in the development and optimization of self-nanoemulsifying drug delivery system for enhanced dissolution of ezetimibe

Fabrication of lipidic nanocarriers of loratadine for facilitated intestinal permeation using multivariate design approach

Preferential Solvation Study of Rosuvastatin in the {PEG400 (1) + Water (2)} Cosolvent Mixture and GastroPlus Software-Based In Vivo Predictions

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