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Cationic Solid SMEDDS of Efavirenz for Improved Oral Delivery: Development by Central Composite Design, In Vitro and In Vivo Evaluation

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Abstract

Efavirenz (EFV) is an anti-HIV drug with high dose and 40% oral bioavailability (BA). The aim was to improve the bioavailability by designing cationic solid SMEDDS. Solubility data, ternary phase diagrams, and central composite design were employed in design. Globule size, TEM, DSC, and SEM studies were used for characterization. Optimized L-SMEDDS contained 20 mg of EFV, 10 mg of Peceol, 43.5 mg of Tween 80, and 40 mg of Labrafac Lipophile WL-1349 and the characters included mean globule size-94 nm, PDI-0.255, and ZP-28 mV. Later, octadecylamine was added to get L-SMEDDS with  + 38 mV charge. L-SMEDDS was converted into solid S-SMEDDS by adsorbing onto silica carriers. Syloid XDP was preferred based on flow and oil adsorption capacity. The % drug (EFV) release from powder, L-SMEDDS, and solid SMEDDS were 14.04, 94.47, and 85 respectively in first 30 min. TEM picture showed dispersed globules. DSC and SEM studies indicated the loss of drug crystallinity in S-SMEDDS. Pharmacokinetic (PK) studies in Wistar rats revealed 4.12 fold hike in BA for optimized cationic S-SMEDDS when compared to EFV suspension. Increased absorption could be due to the positive charge on globules. Thus, cationic S-SMEDDS emerged as a potential novel delivery system for improvement in BA and has scope for reducing the high dose for AIDS patients by future clinical studies.

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Acknowledgements

The authors are indebted to M/s Aizant Drug Research Pvt. Ltd., India for providing drug sample of efavirenz. The authors are also thankful to M/s Abitec Corporation, USA, and M/s Gattefosse, France for supplying free samples of vehicles. The authors are thankful to M/s Fuji Chemicals, Japan, M/s Grace & Co for contributing free samples of solid carriers. And also to M/s ACG associated capsules Pvt. Ltd., India to supply free empty hard gelatin capsules.

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Authors and Affiliations

  1. Department of Nanotechnology, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Telangana, 506009, India

    Sunil Kumar Thota, Narendar Dudhipala, Venumadhav Katla & Kishan Veerabrahma

  2. Department of Pharmaceutics, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Telangana, 506009, India

    Kishan Veerabrahma

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  1. Sunil Kumar Thota
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Contributions

The research idea was proposed by Prof. V. Kishan (corresponding author). The experimental work was carried out by Mr. Thota Sunil Kumar, a master student. Manuscript was drafted by Mr. Thota Sunil Kumar. The animal studies and software applications were supported by Narendar Dudhipala and Venumadhav Katla. Prof. V. Kishan interpreted the data and supervised the study.

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Correspondence to Kishan Veerabrahma.

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Thota, S.K., Dudhipala, N., Katla, V. et al. Cationic Solid SMEDDS of Efavirenz for Improved Oral Delivery: Development by Central Composite Design, In Vitro and In Vivo Evaluation. AAPS PharmSciTech 24, 38 (2023). https://doi.org/10.1208/s12249-022-02495-3

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