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Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach.
AAPS PharmSciTech. 2016 Feb; 17(1):214-32.AP

Abstract

The objective of the study was to identify the extragranular component requirements (level and type of excipients) to develop an immediate release tablet of solid dispersions prepared by hot melt extrusion (HME) process using commonly used HME polymers. Solid dispersions of compound X were prepared using polyvinyl pyrrolidone co-vinyl acetate 64 (PVP VA64), Soluplus, and hypromellose acetate succinate (HPMCAS-LF) polymers in 1:2 ratio by HME through 18 mm extruder. A mixture design was employed to study effect of type of polymer, filler (microcrystalline cellulose (MCC), lactose, and dicalcium phosphate anhydrous (DCPA)), and disintegrant (Crospovidone, croscarmellose sodium, and sodium starch glycolate (SSG)) as well as level of extrudates, filler, and disintegrant on tablet properties such as disintegration time (DT), tensile strength (TS), compactibility, and dissolution. Higher extrudate level resulted in longer DT and lower TS so 60-70% was the maximum amount of acceptable extrudate level in tablets. Fast disintegration was achieved with HPMCAS-containing tablets, whereas Soluplus- and PVP VA64-containing tablets had higher TS. Crospovidone and croscarmellose sodium were more suitable disintegrant than SSG to achieve short DT, and MCC was a suitable filler to prepare tablets with acceptable TS for each studied HME polymer. The influence of extragranular components on dissolution from tablets should be carefully evaluated while finalizing tablet composition, as it varies for each HME polymer. The developed statistical models identified suitable level of fillers and disintegrants for each studied HME polymer to achieve tablets with rapid DT (<15 min) and acceptable TS (≥1 MPa at 10-15% tablet porosity), and their predictivity was confirmed by conducting internal and external validation studies.

Authors+Show Affiliations

Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, Connecticut, 06877, USA. anjali_50@yahoo.com.Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, Connecticut, 06877, USA.Evonik Corporation, 750 Lakeshore Parkway, Birmingham, Alabama, 35211, USA.Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, Connecticut, 06877, USA.Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, Connecticut, 06877, USA.Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, Connecticut, 06877, USA.Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, Connecticut, 06877, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26757898

Citation

Agrawal, Anjali, et al. "Development of Tablet Formulation of Amorphous Solid Dispersions Prepared By Hot Melt Extrusion Using Quality By Design Approach." AAPS PharmSciTech, vol. 17, no. 1, 2016, pp. 214-32.
Agrawal A, Dudhedia M, Deng W, et al. Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach. AAPS PharmSciTech. 2016;17(1):214-32.
Agrawal, A., Dudhedia, M., Deng, W., Shepard, K., Zhong, L., Povilaitis, E., & Zimny, E. (2016). Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach. AAPS PharmSciTech, 17(1), 214-32. https://doi.org/10.1208/s12249-015-0472-0
Agrawal A, et al. Development of Tablet Formulation of Amorphous Solid Dispersions Prepared By Hot Melt Extrusion Using Quality By Design Approach. AAPS PharmSciTech. 2016;17(1):214-32. PubMed PMID: 26757898.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach. AU - Agrawal,Anjali, AU - Dudhedia,Mayur, AU - Deng,Weibin, AU - Shepard,Kevin, AU - Zhong,Li, AU - Povilaitis,Edward, AU - Zimny,Ewa, Y1 - 2016/01/12/ PY - 2015/09/01/received PY - 2015/12/17/accepted PY - 2016/1/14/entrez PY - 2016/1/14/pubmed PY - 2016/12/15/medline KW - amorphous KW - disintegrant KW - filler KW - hot melt extrusion KW - solid dispersion KW - tablet SP - 214 EP - 32 JF - AAPS PharmSciTech JO - AAPS PharmSciTech VL - 17 IS - 1 N2 - The objective of the study was to identify the extragranular component requirements (level and type of excipients) to develop an immediate release tablet of solid dispersions prepared by hot melt extrusion (HME) process using commonly used HME polymers. Solid dispersions of compound X were prepared using polyvinyl pyrrolidone co-vinyl acetate 64 (PVP VA64), Soluplus, and hypromellose acetate succinate (HPMCAS-LF) polymers in 1:2 ratio by HME through 18 mm extruder. A mixture design was employed to study effect of type of polymer, filler (microcrystalline cellulose (MCC), lactose, and dicalcium phosphate anhydrous (DCPA)), and disintegrant (Crospovidone, croscarmellose sodium, and sodium starch glycolate (SSG)) as well as level of extrudates, filler, and disintegrant on tablet properties such as disintegration time (DT), tensile strength (TS), compactibility, and dissolution. Higher extrudate level resulted in longer DT and lower TS so 60-70% was the maximum amount of acceptable extrudate level in tablets. Fast disintegration was achieved with HPMCAS-containing tablets, whereas Soluplus- and PVP VA64-containing tablets had higher TS. Crospovidone and croscarmellose sodium were more suitable disintegrant than SSG to achieve short DT, and MCC was a suitable filler to prepare tablets with acceptable TS for each studied HME polymer. The influence of extragranular components on dissolution from tablets should be carefully evaluated while finalizing tablet composition, as it varies for each HME polymer. The developed statistical models identified suitable level of fillers and disintegrants for each studied HME polymer to achieve tablets with rapid DT (<15 min) and acceptable TS (≥1 MPa at 10-15% tablet porosity), and their predictivity was confirmed by conducting internal and external validation studies. SN - 1530-9932 UR - https://www.unboundmedicine.com/medline/citation/26757898/Development_of_Tablet_Formulation_of_Amorphous_Solid_Dispersions_Prepared_by_Hot_Melt_Extrusion_Using_Quality_by_Design_Approach_ L2 - https://dx.doi.org/10.1208/s12249-015-0472-0 DB - PRIME DP - Unbound Medicine ER -