Microstructural imaging of early gel layer formation in HPMC matrices.
A real-time confocal fluorescence imaging method has been developed which allows the critical early stages of gel layer formation in hydroxypropylmethylcellulose (HPMC) matrices to be examined. Congo Red, a fluorophore whose fluorescence is selectively intensified when bound to beta-D-glucopyranosyl sequences, has allowed mapping of hydrated polymer regions within the emerging gel layer, and revealed for the first time, the microstructural sequence of polymer hydration during development of the early gel layer. Liquid penetration and swelling can be examined in unprecedented detail. The earliest images revealed an initial phase of liquid ingress into the tablet pore network, followed by the progressive formation of a coherent gel layer by outward columnar swelling and coalescence of hydrated HPMC particles. Salts can markedly affect HPMC matrix behaviour. Gel layer growth in 0.1-0.5 M NaCl was progressively suppressed until at 0.75 M, particles clearly failed to coalesce into a gel layer, although with considerable polymer swelling. The failure to form a limiting diffusion barrier resulted in enhanced liquid penetration of the core, and the swelling of particles that did not coalesce culminated in surface disintegration. This provides direct evidence of physical mechanisms that contribute to salts accelerating drug release from HPMC matrices.
Bajwa
Gurjit S
GS
Formulation Insights, School of Pharmacy, University of Nottingham, NG7 2RD UK.
Hoebler
Katrin
K
Sammon
Chris
C
Timmins
Peter
P
Melia
Colin D
CD
D003224:Congo Red / Q000737:chemistry; D004339:Drug Compounding; D004355:Drug Stability; D005782:Gels / Q000737:chemistry*; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D018613:Microscopy, Confocal; D018715:Microscopy, Video; D009391:Nephelometry and Turbidimetry; D012965:Sodium Chloride / Q000737:chemistry; D014867:Water / Q000737:chemistry
D005782:Gels; D014867:Water; D065347:Hypromellose Derivatives; D003224:Congo Red; D012965:Sodium Chloride; D008747:Methylcellulose