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Roller compaction, granulation and capsule product dissolution of drug formulations containing a lactose or mannitol filler, starch, and talc.
AAPS PharmSciTech. 2008; 9(2):597-604.AP

Abstract

This study investigated the influence of excipient composition to the roller compaction and granulation characteristics of pharmaceutical formulations that were comprised of a spray-dried filler (lactose monohydrate or mannitol), pregelatinized starch, talc, magnesium stearate (1% w/w) and a ductile active pharmaceutical ingredient (25% w/w) using a mixed-level factorial design. The main and interaction effects of formulation variables (i.e., filler type, starch content, and talc content) to the response factors (i.e., solid fraction and tensile strength of ribbons, particle size, compressibility and flow of granules) were analyzed using multi-linear stepwise regression analysis. Experimental results indicated that roller compacted ribbons of both lactose and mannitol formulations had similar tensile strength. However, resulting lactose-based granules were finer than the mannitol-based granules because of the brittleness of lactose compared to mannitol. Due to the poor compressiblility of starch, increasing starch content in the formulation from 0% to 20% w/w led to reduction in ribbon solid fraction by 10%, ribbon tensile strength by 60%, and granule size by 30%. Granules containing lactose or more starch showed less cohesive flow than granules containing mannitol and less starch. Increasing talc content from 0% to 5% w/w had little effect to most physical properties of ribbons and granules while the flow of mannitol-based granules was found improved. Finally, it was observed that stored at 40 degrees C/75% RH over 12 weeks, gelatin capsules containing lactose-based granules had reduced dissolution rates due to pellicle formation inside capsule shells, while capsules containing mannitol-based granules remained immediate dissolution without noticeable pellicle formation.

Authors+Show Affiliations

Pfizer Global Research and Development, Pfizer Inc., Ann Arbor, Michigan 48105, USA. chialuc@amgen.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18459052

Citation

Chang, Chialu Kevin, et al. "Roller Compaction, Granulation and Capsule Product Dissolution of Drug Formulations Containing a Lactose or Mannitol Filler, Starch, and Talc." AAPS PharmSciTech, vol. 9, no. 2, 2008, pp. 597-604.
Chang CK, Alvarez-Nunez FA, Rinella JV, et al. Roller compaction, granulation and capsule product dissolution of drug formulations containing a lactose or mannitol filler, starch, and talc. AAPS PharmSciTech. 2008;9(2):597-604.
Chang, C. K., Alvarez-Nunez, F. A., Rinella, J. V., Magnusson, L. E., & Sueda, K. (2008). Roller compaction, granulation and capsule product dissolution of drug formulations containing a lactose or mannitol filler, starch, and talc. AAPS PharmSciTech, 9(2), 597-604. https://doi.org/10.1208/s12249-008-9088-y
Chang CK, et al. Roller Compaction, Granulation and Capsule Product Dissolution of Drug Formulations Containing a Lactose or Mannitol Filler, Starch, and Talc. AAPS PharmSciTech. 2008;9(2):597-604. PubMed PMID: 18459052.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Roller compaction, granulation and capsule product dissolution of drug formulations containing a lactose or mannitol filler, starch, and talc. AU - Chang,Chialu Kevin, AU - Alvarez-Nunez,Fernando A, AU - Rinella,Joseph V,Jr AU - Magnusson,Lars-Erik, AU - Sueda,Katsuhiko, Y1 - 2008/05/06/ PY - 2007/09/11/received PY - 2008/03/24/accepted PY - 2008/5/7/pubmed PY - 2008/9/16/medline PY - 2008/5/7/entrez SP - 597 EP - 604 JF - AAPS PharmSciTech JO - AAPS PharmSciTech VL - 9 IS - 2 N2 - This study investigated the influence of excipient composition to the roller compaction and granulation characteristics of pharmaceutical formulations that were comprised of a spray-dried filler (lactose monohydrate or mannitol), pregelatinized starch, talc, magnesium stearate (1% w/w) and a ductile active pharmaceutical ingredient (25% w/w) using a mixed-level factorial design. The main and interaction effects of formulation variables (i.e., filler type, starch content, and talc content) to the response factors (i.e., solid fraction and tensile strength of ribbons, particle size, compressibility and flow of granules) were analyzed using multi-linear stepwise regression analysis. Experimental results indicated that roller compacted ribbons of both lactose and mannitol formulations had similar tensile strength. However, resulting lactose-based granules were finer than the mannitol-based granules because of the brittleness of lactose compared to mannitol. Due to the poor compressiblility of starch, increasing starch content in the formulation from 0% to 20% w/w led to reduction in ribbon solid fraction by 10%, ribbon tensile strength by 60%, and granule size by 30%. Granules containing lactose or more starch showed less cohesive flow than granules containing mannitol and less starch. Increasing talc content from 0% to 5% w/w had little effect to most physical properties of ribbons and granules while the flow of mannitol-based granules was found improved. Finally, it was observed that stored at 40 degrees C/75% RH over 12 weeks, gelatin capsules containing lactose-based granules had reduced dissolution rates due to pellicle formation inside capsule shells, while capsules containing mannitol-based granules remained immediate dissolution without noticeable pellicle formation. SN - 1530-9932 UR - https://www.unboundmedicine.com/medline/citation/18459052/Roller_compaction_granulation_and_capsule_product_dissolution_of_drug_formulations_containing_a_lactose_or_mannitol_filler_starch_and_talc_ L2 - https://dx.doi.org/10.1208/s12249-008-9088-y DB - PRIME DP - Unbound Medicine ER -