Tags

Type your tag names separated by a space and hit enter

Direct compression tablets containing a series of four beta-cyclodextrin complexes formed by neutralizing an acidic drug.
Drug Dev Ind Pharm. 2000 Dec; 26(12):1259-70.DD

Abstract

A series of four beta-cyclodextrin complexes (called products) was formed by neutralizing an acidic drug to study the effect of drug solubility on complex formation and the dissolution performance from direct compression tablets. Four solid products were prepared by neutralizing the drug in 0.05, 0.10, 0.20, and 0.30 M tromethamine solutions with a constant 0.09 M beta-cyclodextrin concentration, filtering the solutions, and removing the water through evaporation with heat and vacuum. The four products contained drug and water in a distinct relationship, thus suggesting a complex formation that was dependent on the tromethamine concentration. Infrared, powder X-ray diffraction, differential scanning calorimetry (DSC), phase solubility, and scanning electron microscopy (SEM) techniques revealed distinct differences among the four products, suggesting three of the four products were complexes, and one product was either a weak complex or a physical mixture. Ultraviolet (UV) analysis showed no evidence of complex formation. Phase solubility results showed one product had a slight increase in drug solubility, and three products had no increase in drug solubility with increasing beta-cyclodextrin concentration. The lack of a solubility increase suggests insoluble complex formation. Drug dissolution in water was improved significantly in all tablets containing either a product or a physical mixture when compared to the pure drug. The products prepared with the two highest concentrations of tromethamine showed a dissolution performance that was superior to all other formulations. Enthalpy measurements by DSC were a good indicator of dissolution performance for tablets containing the four products. Drug dissolution through salt formation in the absence of beta-cyclodextrin showed the drug-salt dissolution varied from better to worse when compared to the dissolution profiles of the four products. The varying dissolution performance was attributed to the formation of distinct beta-cyclodextrin complexes with varing solubilities.

Authors+Show Affiliations

AstraZeneca, a Business Unit of Zeneca, Incorporated, 1800 Concord Pike, Wilmington, DE 19850-5437.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11147126

Citation

Moore, E, et al. "Direct Compression Tablets Containing a Series of Four Beta-cyclodextrin Complexes Formed By Neutralizing an Acidic Drug." Drug Development and Industrial Pharmacy, vol. 26, no. 12, 2000, pp. 1259-70.
Moore E, Bergamo R, Casella R. Direct compression tablets containing a series of four beta-cyclodextrin complexes formed by neutralizing an acidic drug. Drug Dev Ind Pharm. 2000;26(12):1259-70.
Moore, E., Bergamo, R., & Casella, R. (2000). Direct compression tablets containing a series of four beta-cyclodextrin complexes formed by neutralizing an acidic drug. Drug Development and Industrial Pharmacy, 26(12), 1259-70.
Moore E, Bergamo R, Casella R. Direct Compression Tablets Containing a Series of Four Beta-cyclodextrin Complexes Formed By Neutralizing an Acidic Drug. Drug Dev Ind Pharm. 2000;26(12):1259-70. PubMed PMID: 11147126.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Direct compression tablets containing a series of four beta-cyclodextrin complexes formed by neutralizing an acidic drug. AU - Moore,E, AU - Bergamo,R, AU - Casella,R, PY - 2001/1/9/pubmed PY - 2001/3/7/medline PY - 2001/1/9/entrez SP - 1259 EP - 70 JF - Drug development and industrial pharmacy JO - Drug Dev Ind Pharm VL - 26 IS - 12 N2 - A series of four beta-cyclodextrin complexes (called products) was formed by neutralizing an acidic drug to study the effect of drug solubility on complex formation and the dissolution performance from direct compression tablets. Four solid products were prepared by neutralizing the drug in 0.05, 0.10, 0.20, and 0.30 M tromethamine solutions with a constant 0.09 M beta-cyclodextrin concentration, filtering the solutions, and removing the water through evaporation with heat and vacuum. The four products contained drug and water in a distinct relationship, thus suggesting a complex formation that was dependent on the tromethamine concentration. Infrared, powder X-ray diffraction, differential scanning calorimetry (DSC), phase solubility, and scanning electron microscopy (SEM) techniques revealed distinct differences among the four products, suggesting three of the four products were complexes, and one product was either a weak complex or a physical mixture. Ultraviolet (UV) analysis showed no evidence of complex formation. Phase solubility results showed one product had a slight increase in drug solubility, and three products had no increase in drug solubility with increasing beta-cyclodextrin concentration. The lack of a solubility increase suggests insoluble complex formation. Drug dissolution in water was improved significantly in all tablets containing either a product or a physical mixture when compared to the pure drug. The products prepared with the two highest concentrations of tromethamine showed a dissolution performance that was superior to all other formulations. Enthalpy measurements by DSC were a good indicator of dissolution performance for tablets containing the four products. Drug dissolution through salt formation in the absence of beta-cyclodextrin showed the drug-salt dissolution varied from better to worse when compared to the dissolution profiles of the four products. The varying dissolution performance was attributed to the formation of distinct beta-cyclodextrin complexes with varing solubilities. SN - 0363-9045 UR - https://www.unboundmedicine.com/medline/citation/11147126/Direct_compression_tablets_containing_a_series_of_four_beta_cyclodextrin_complexes_formed_by_neutralizing_an_acidic_drug_ L2 - http://www.tandfonline.com/doi/full/10.1081/ddc-100102307 DB - PRIME DP - Unbound Medicine ER -