Dissolution Effect of Gastric and Intestinal pH fora BCS class II drug, Pioglitazone: New in vitro Dissolution System to Predict in vivo Dissolution

Objective: The aim of this investigation was to enhance the solubility and bioavailability of the BCS class II poorly water-soluble drug ambrisentan by solid dispersion (SD) techniques using Gelucire 50/13 as a hydrophilic carrier. Methods: Solid dispersion of ambrisentan was prepared by kneading method using different dug: carrier ratios. Prepared SD was characterized for solubility, drug content, percentage yield, in vitro dissolution, ex vivo permeation and bioavailability. Solid-state characterization was performed by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Results: All the SDs formulations showed increase in drug solubility and dissolution when compared with its pure form. Aqueous solubility of the drug was found to be increased 8.23 fold in SD. DSC study showed that endothermic peak of the drug was disappeared in spectra of SD, confirming its amorphous conversion, XRD study revealed the reduction to almost absence of specific high-intensity peaks of drug which confirmed the reduction of crysatallinity of ambrisentan in SD. SEM of optimized SD formulation demonstrates the complete encapsulation and solubilization drug. In vitro dissolution study showed that optimized SD formulation (ASD4) gives the faster drug release of 101.5% in 60 min, as compare to its pure form and other SD formulations. Conclusion: Solid dispersion ASD4 prepared with 1:4 drug to carrier ratio showed the highest drug solubility and in vitro dissolution. The ex vivo and in vivo studies performed on optimized formulation ASD4 showed enhancement in drug permeability and bioavailability in Gelucire 50/13 based SD formulation.

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Improved Bioavailability of Oxcarbazepine, a BCS class II drug by Centrifugal Melt Spinning: In-vitro and in-vivo Implications

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2021.120775 ◽

2021 ◽

pp. 120775

Author(s):

Sidra Nasir ◽

Amjad Hussain ◽

Nasir Abbas ◽

Nadeem Irfan Bukhari ◽

Fahad Hussain ◽

...

Keyword(s):

Melt Spinning ◽

Class Ii ◽

Bcs Class Ii

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Development of Level A In Vitro–Vivo Correlation for Electrosprayed Microspheres Containing Leuprolide: Physicochemical, Pharmacokinetic, and Pharmacodynamic Evaluation

Pharmaceutics ◽

10.3390/pharmaceutics12010036 ◽

2020 ◽

Vol 12 (1) ◽

pp. 36

Author(s):

Dong-Seok Lee ◽

Dong Wook Kang ◽

Go-Wun Choi ◽

Han-Gon Choi ◽

Hea-Young Cho

Keyword(s):

Plasma Concentration ◽

Prediction Error ◽

Subcutaneous Administration ◽

In Vitro Dissolution ◽

Burst Release ◽

Maximum Plasma ◽

Time Curve ◽

In Vivo Dissolution

This study optimized the preparation of electrosprayed microspheres containing leuprolide and developed an in vitro–in vivo correlation (IVIVC) model that enables mutual prediction between in vitro and in vivo dissolution. The pharmacokinetic (PK) and pharmacodynamic (PD) study of leuprolide was carried out in normal rats after subcutaneous administration of electrosprayed microspheres. The parameters of the IVIVC model were estimated by fitting the PK profile of Lucrin depot® to the release compartment of the IVIVC model, thus the in vivo dissolution was predicted from the in vitro dissolution. From this correlation, the PK profile of leuprolide was predicted from the results of in vivo dissolution. The IVIVC model was validated by estimating percent prediction error (%PE) values. Among prepared microspheres, an optimal formulation was selected using the IVIVC model. The maximum plasma concentration and the area under the plasma concentration–time curve from zero to infinity from the predicted PK profile were 4.01 ng/mL and 52.52 h·ng/mL, respectively, and from the observed PK profile were 4.14 ng/mL and 56.95 h·ng/mL, respectively. The percent prediction error values of all parameters did not exceed 15%, thus the IVIVC model satisfies the validation criteria of the Food and Drug Administration (FDA) guidance. The PK/PD evaluation suggests that the efficacy of OL5 is similar to Lucrin depot®, but the formulation was improved by reducing the initial burst release.

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Improved Efficacy of Lovastatin from Soluplus-PEG Hybrid Polymer- Based Binary Dispersions

Current Bioactive Compounds ◽

10.2174/1573407216666191218142852 ◽

2020 ◽

Vol 16 (8) ◽

pp. 1164-1171

Author(s):

Radhika Verma ◽

Manju Nagpal ◽

Thakur G. Singh ◽

Manjinder Singh ◽

Geeta Aggarwal

Keyword(s):

Drug Release ◽

Solid Dispersions ◽

Class Ii ◽

Hybrid Polymer ◽

In Vitro Drug Release ◽

In Vivo Efficacy ◽

Bcs Class Ii ◽

Individual Polymer

Background: Lovastatin is a statin drug used for lowering cholesterol in those with hypercholesterolemia to reduce the risk of cardiovascular disease. It is a BCS class II drug i.e. it has low aqueous solubility and high permeability. Objective: Improvement of solubility and in vivo efficacy was investigated by formulating binary solid dispersions. Methods: Binary solid dispersions of lovastatin were formulated in the current study using two polymers i.e. Soluplus and PEG 4000. Seven batches of solid dispersions were prepared (S1, P1, SP1, SP2, SP3, SP4, and SP5) via the solvent evaporation method. The prepared dispersions were evaluated for equilibrium solubility, FTIR, XRD, DSC, SEM studies, and further in vitro drug release were evaluated. The results revealed significant enhancement in the solubility of drug-using polymer hybrids as compared to that of individual polymer dispersion batches. Results: A significant solubility enhancement was observed with SP5 (approx 40 times) having a higher concentration of Soluplus. FTIR studies indicated no drug to polymer interaction. DSC studies revealed complete amorphization of polymer and also X-RD data is also in compliance with DSC results. In vitro drug release studies showed almost 100% release in 2h in polymer hybrid batches in comparison to individual polymer batch (S1 and P1). The best dissolution characteristics were observed in SP3 and SP5 which is also in compliance with solubility data. Further in vivo efficacy studies revealed a significant reduction in LDL, HDL, TG, AST, and ALT levels in comparison to pure drug lovastatin group and hypercholesterolemia control group. Conclusion: Hybrid polymer may be a prospective carrier system for the enhancement of solubility of BCS class II drugs.

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