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Amorphous solid dispersion of nisoldipine by solvent evaporation technique: preparation, characterization, in vitro, in vivo evaluation, and scale up feasibility study.
Drug Deliv Transl Res. 2020 08; 10(4):903-918.DD

Abstract

The present study was designed to determine the applicability of a newly derived dimensionless number precipitation parameter, "supersaturation holding capacity (SHC)" in development of amorphous solid dispersion (ASD) of a rapidly crystallizing drug, nisoldipine. Also, ASD preparation from lab scale formulation technique to scalable spray drying technique followed by oral bioavailability study was demonstrated. Solution state screening of polymers was performed by determining nucleation induction time (tin) and SHC. With screened polymers, lab scale ASDs of nisoldipine were prepared using rotary evaporation (solvent evaporation) method, and the optimized stable ASDs were scaled up by spray drying. The ASDs were characterized by DSC, PXRD, and FTIR for amorphous nature and evaluated for apparent solubility, dissolution, and solid-state stability improvement. The spray dried ASDs were additionally evaluated for micrometric properties and oral bioavailability study.PVP grades demonstrated superior crystal growth inhibition properties (with 2-4-fold enhancements in SHC). ASDs prepared by both lab scale and scale-up technique using PVP stabilized the amorphous nisoldipine via antiplasticization effect that maintained the stability under accelerated stability conditions (40 °C/75% RH) for 6 months. Additionally, FTIR study confirmed the role of intermolecular interactions in amorphous state stabilization of PVP-based solid dispersions. PVP-based spray dried ASDs improved the apparent solubility 4-fold for PVP K17 and more than 3-fold for remaining spray dried ASDs. The enhanced solubility was translated to improved dissolution of the drug when compared with crystalline and amorphous form complementing the outcome of the solution state study. The spray dried ASD showed 2.3 and > 3-fold the improvement in Cmax and AUC (0-24 h) respectively when compared with crystalline nisoldipine during oral bioavailability study which highlights the significance of SHC parameter of polymers. The spray dried ASD has shown improved micromeritics properties then crystalline nisoldipine in terms of flow behavior.This unique study provides a rational strategy for selection of appropriate polymer in development of ASDs that can tackle both precipitation during dissolution and amorphous state stabilization in solid state and also considers the SHC in scale-up study. Graphical abstract.

Authors+Show Affiliations

Solid State Pharmaceutical Research Group (SSPRG), Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, 500037, India.Solid State Pharmaceutical Research Group (SSPRG), Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, 500037, India.Solid State Pharmaceutical Research Group (SSPRG), Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, 500037, India.Solid State Pharmaceutical Research Group (SSPRG), Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, 500037, India. nalini.niperhyd@gmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32378174

Citation

Chavan, Rahul B., et al. "Amorphous Solid Dispersion of Nisoldipine By Solvent Evaporation Technique: Preparation, Characterization, in Vitro, in Vivo Evaluation, and Scale Up Feasibility Study." Drug Delivery and Translational Research, vol. 10, no. 4, 2020, pp. 903-918.
Chavan RB, Lodagekar A, Yadav B, et al. Amorphous solid dispersion of nisoldipine by solvent evaporation technique: preparation, characterization, in vitro, in vivo evaluation, and scale up feasibility study. Drug Deliv Transl Res. 2020;10(4):903-918.
Chavan, R. B., Lodagekar, A., Yadav, B., & Shastri, N. R. (2020). Amorphous solid dispersion of nisoldipine by solvent evaporation technique: preparation, characterization, in vitro, in vivo evaluation, and scale up feasibility study. Drug Delivery and Translational Research, 10(4), 903-918. https://doi.org/10.1007/s13346-020-00775-8
Chavan RB, et al. Amorphous Solid Dispersion of Nisoldipine By Solvent Evaporation Technique: Preparation, Characterization, in Vitro, in Vivo Evaluation, and Scale Up Feasibility Study. Drug Deliv Transl Res. 2020;10(4):903-918. PubMed PMID: 32378174.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amorphous solid dispersion of nisoldipine by solvent evaporation technique: preparation, characterization, in vitro, in vivo evaluation, and scale up feasibility study. AU - Chavan,Rahul B, AU - Lodagekar,Anurag, AU - Yadav,Balvant, AU - Shastri,Nalini R, PY - 2020/5/8/pubmed PY - 2021/8/3/medline PY - 2020/5/8/entrez KW - Amorphous system KW - DSC spray drying KW - Glass transition temperature KW - Precipitation KW - Supersaturation SP - 903 EP - 918 JF - Drug delivery and translational research JO - Drug Deliv Transl Res VL - 10 IS - 4 N2 - The present study was designed to determine the applicability of a newly derived dimensionless number precipitation parameter, "supersaturation holding capacity (SHC)" in development of amorphous solid dispersion (ASD) of a rapidly crystallizing drug, nisoldipine. Also, ASD preparation from lab scale formulation technique to scalable spray drying technique followed by oral bioavailability study was demonstrated. Solution state screening of polymers was performed by determining nucleation induction time (tin) and SHC. With screened polymers, lab scale ASDs of nisoldipine were prepared using rotary evaporation (solvent evaporation) method, and the optimized stable ASDs were scaled up by spray drying. The ASDs were characterized by DSC, PXRD, and FTIR for amorphous nature and evaluated for apparent solubility, dissolution, and solid-state stability improvement. The spray dried ASDs were additionally evaluated for micrometric properties and oral bioavailability study.PVP grades demonstrated superior crystal growth inhibition properties (with 2-4-fold enhancements in SHC). ASDs prepared by both lab scale and scale-up technique using PVP stabilized the amorphous nisoldipine via antiplasticization effect that maintained the stability under accelerated stability conditions (40 °C/75% RH) for 6 months. Additionally, FTIR study confirmed the role of intermolecular interactions in amorphous state stabilization of PVP-based solid dispersions. PVP-based spray dried ASDs improved the apparent solubility 4-fold for PVP K17 and more than 3-fold for remaining spray dried ASDs. The enhanced solubility was translated to improved dissolution of the drug when compared with crystalline and amorphous form complementing the outcome of the solution state study. The spray dried ASD showed 2.3 and > 3-fold the improvement in Cmax and AUC (0-24 h) respectively when compared with crystalline nisoldipine during oral bioavailability study which highlights the significance of SHC parameter of polymers. The spray dried ASD has shown improved micromeritics properties then crystalline nisoldipine in terms of flow behavior.This unique study provides a rational strategy for selection of appropriate polymer in development of ASDs that can tackle both precipitation during dissolution and amorphous state stabilization in solid state and also considers the SHC in scale-up study. Graphical abstract. SN - 2190-3948 UR - https://www.unboundmedicine.com/medline/citation/32378174/Amorphous_solid_dispersion_of_nisoldipine_by_solvent_evaporation_technique:_preparation_characterization_in_vitro_in_vivo_evaluation_and_scale_up_feasibility_study_ L2 - https://dx.doi.org/10.1007/s13346-020-00775-8 DB - PRIME DP - Unbound Medicine ER -