Enhancing and sustaining AMG 009 dissolution from a bilayer oral solid dosage form via microenvironmental pH modulation and supersaturation.
Enhancing and sustaining AMG 009 dissolution from a matrix tablet via microenvironmental pH modulation and supersaturation, where poorly soluble acidic AMG 009 molecule was intimately mixed and compressed together with a basic pH modifier (e.g., sodium carbonate) and nucleation inhibitor hydroxypropyl methylcellulose K100 LV (HPMC K100 LV), was demonstrated previously. However, not all acidic or basic drugs are compatible with basic or acidic pH modifiers either chemically or physically. The objective of this study is to investigate whether similar dissolution enhancement of AMG 009 can be achieved from a bilayer dosage form, where AMG 009 and sodium carbonate are placed in a separate layer with or without the addition of HPMC K100 LV in each layer. Study results indicate that HPMC K100 LV-containing bilayer dosage forms gained similar dissolution enhancement as matrix dosage forms did. Bilayer dosage forms without HPMC K100 LV benefitted the least from dissolution enhancement.
Formulation Group, Pharmaceutical R&D, Amgen Inc, Thousand Oaks, California 91320, USA. mbi@amgen.com
Mingda
M
Bi
Ali
A
Kyad
Fernando
F
Alvarez-Nunez
Francisco
F
Alvarez
D000284:Administration, Oral; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry*; D002214:Capsules; D002254:Carbonates / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D010648:Phenylacetates / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D013449:Sulfonamides / Q000008:administration & dosage / Q000737:chemistry*; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods
C570879:AMG 009; D000893:Anti-Inflammatory Agents; D002214:Capsules; D002254:Carbonates; D010648:Phenylacetates; D013449:Sulfonamides; D013607:Tablets; D065347:Hypromellose Derivatives; C005686:sodium carbonate; D008747:Methylcellulose