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Effect of a melt agglomeration process on agglomerates containing solid dispersions.
Int J Pharm. 2005 Oct 13; 303(1-2):132-42.IJ

Abstract

The purpose was to produce solid dispersions of a poorly water-soluble drug, Lu-X, by melt agglomeration in a laboratory scale rotary processor. The effect of binder type and method of manufacturing on the dissolution profile of Lu-X was investigated. Lactose monohydrate and Lu-X were melt agglomerated with Rylo MG12, Gelucire 50/13, PEG 3000, or poloxamer 188. Either a mixture of binder, drug, and excipient was heated to a temperature above the melting point of the binder (melt-in procedure) or a dispersion of drug in molten binder was sprayed on the heated excipient (spray-on procedure). The agglomerates were characterized by DSC, XRPD, SEM, and EDX-SEM. The study showed that the agglomerates containing solid dispersions had improved dissolution rates compared to physical mixtures and pure drug. The melt-in procedure gave a higher dissolution rate than the spray-on procedure with PEG 3000, poloxamer 188, and Gelucire 50/13, whereas the opposite was found with Rylo MG12. This was explained by differences in mechanisms of agglomerate formation and growth, which were dominated by immersion with PEG 3000, poloxamer 188, and Gelucire 50/13, and by distribution and coalescence with Rylo MG12. The spray-on procedure resulted in a higher content of Lu-X in the core of the agglomerates when immersion was the dominating mechanism, and in a higher content in the agglomerate surface when distribution was dominating. The melt-in procedure resulted generally in a homogeneous distribution of Lu-X in the agglomerates. The compounds in the agglomerates were found primarily to be crystalline, and the dissolution profiles were unchanged after 12 weeks storage at 25 degrees C at 50% RH.

Authors+Show Affiliations

The Danish University of Pharmaceutical Sciences, Department of Pharmaceutics, 2 Universitetsparken, DK-2100 Copenhagen, Denmark.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16139973

Citation

Vilhelmsen, Thomas, et al. "Effect of a Melt Agglomeration Process On Agglomerates Containing Solid Dispersions." International Journal of Pharmaceutics, vol. 303, no. 1-2, 2005, pp. 132-42.
Vilhelmsen T, Eliasen H, Schaefer T. Effect of a melt agglomeration process on agglomerates containing solid dispersions. Int J Pharm. 2005;303(1-2):132-42.
Vilhelmsen, T., Eliasen, H., & Schaefer, T. (2005). Effect of a melt agglomeration process on agglomerates containing solid dispersions. International Journal of Pharmaceutics, 303(1-2), 132-42.
Vilhelmsen T, Eliasen H, Schaefer T. Effect of a Melt Agglomeration Process On Agglomerates Containing Solid Dispersions. Int J Pharm. 2005 Oct 13;303(1-2):132-42. PubMed PMID: 16139973.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of a melt agglomeration process on agglomerates containing solid dispersions. AU - Vilhelmsen,Thomas, AU - Eliasen,Helle, AU - Schaefer,Torben, PY - 2005/02/11/received PY - 2005/06/30/revised PY - 2005/07/13/accepted PY - 2005/9/6/pubmed PY - 2006/4/14/medline PY - 2005/9/6/entrez SP - 132 EP - 42 JF - International journal of pharmaceutics JO - Int J Pharm VL - 303 IS - 1-2 N2 - The purpose was to produce solid dispersions of a poorly water-soluble drug, Lu-X, by melt agglomeration in a laboratory scale rotary processor. The effect of binder type and method of manufacturing on the dissolution profile of Lu-X was investigated. Lactose monohydrate and Lu-X were melt agglomerated with Rylo MG12, Gelucire 50/13, PEG 3000, or poloxamer 188. Either a mixture of binder, drug, and excipient was heated to a temperature above the melting point of the binder (melt-in procedure) or a dispersion of drug in molten binder was sprayed on the heated excipient (spray-on procedure). The agglomerates were characterized by DSC, XRPD, SEM, and EDX-SEM. The study showed that the agglomerates containing solid dispersions had improved dissolution rates compared to physical mixtures and pure drug. The melt-in procedure gave a higher dissolution rate than the spray-on procedure with PEG 3000, poloxamer 188, and Gelucire 50/13, whereas the opposite was found with Rylo MG12. This was explained by differences in mechanisms of agglomerate formation and growth, which were dominated by immersion with PEG 3000, poloxamer 188, and Gelucire 50/13, and by distribution and coalescence with Rylo MG12. The spray-on procedure resulted in a higher content of Lu-X in the core of the agglomerates when immersion was the dominating mechanism, and in a higher content in the agglomerate surface when distribution was dominating. The melt-in procedure resulted generally in a homogeneous distribution of Lu-X in the agglomerates. The compounds in the agglomerates were found primarily to be crystalline, and the dissolution profiles were unchanged after 12 weeks storage at 25 degrees C at 50% RH. SN - 0378-5173 UR - https://www.unboundmedicine.com/medline/citation/16139973/Effect_of_a_melt_agglomeration_process_on_agglomerates_containing_solid_dispersions_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(05)00500-4 DB - PRIME DP - Unbound Medicine ER -