Imaging of the Effect of Alcohol-Containing Media on the Performance of Hypromellose Hydrophilic Matrix Tablets: Comparison of Direct Compression and Regular Grades of Polymer

Abstract

As the ingestion of drug products with alcohol could have adverse effects on the release of drugs from dosage forms, it is important to understand the mechanisms underpinning the influence on drug release by evaluating the effect of alcohol-containing media on the behaviour of pharmaceutical excipients. In this work, the effect of hydroalcoholic media containing up to 40% v/v absolute ethanol was evaluated, employing both the regular (CR) and direct compression grades (DC) of hypromellose. X-ray microtomography (XµT) and magnetic resonance imaging (MRI) were used as complementary techniques in determining the influence of the media composition on the ability of the CR and DC polymers to form and evolve the gel layer that controls drug release. Particle and powder properties of the polymer were characterised to determine any relationship to performance in hydroalcoholic media. Triboelectrification results showed the CR grade formulation to charge electropositively whereas the DC grade charged electronegatively. The flow properties also showed the DC grade to have a superior flow as compared to its CR counterpart. Differences in particle morphology between the grades influenced charging and flow behaviour of the powders; however, it did not seem to impact significantly either on the mechanical strength or the drug release properties of the compacted formulation using the model drug propranolol HCl. XµT and MRI imaging were successfully used as complementary techniques in determining the gel layer/hydration layer thickness measurements as the layer developed, as well as following ingress of hydroalcoholic media and its impact on the dry core. The result showed that although differences were present in the gel layer thickness potentially due to differences in particle morphology, this also did not impact significantly on the dissolution process, especially in acidic and hydroalcoholic media.

Application of UV dissolution imaging to pharmaceutical systems

“…Hydrophilic swellable polymers often used include HPMC, poly(ethylene oxide) and hydroxypropylcellulose (HPC) (27). Upon exposure to water or biological fluids, the hydrophilic polymer becomes hydrated, swells and forms a gel layer around an initially dry core ( 184), (195), (196), (197), (198).…”

“…Raman imaging has been used to assess excipient distribution within a tablet (19), (20) for chemical imaging of nasal spray suspensions and API distribution within a tablet (21), (22). NMR/MRI has been used to study the internal mechanisms of the in vitro drug release in dosage forms such as the ingress of dissolution media (23), (24), (25), (26), (27), water distribution in extrudates (28), water diffusion coefficients and polymer concentrations (29), (30), (31), (32), water penetration in osmotic pumps (33), homogeneity in powder mixtures (34), the tablet disintegration process (35), internal barriers for zero-order release systems (36), pulsatile capsules (37) and mapping the distribution of porosity in compacts (38). XµT has been used to measure/assess heterogeneity of powder beds (39), (40), density variations in compacts (41), (42) with and without embossed features (43), (44), porosity of hot-melt extrudates (45), compression characteristic of dry coated tablets (46), packing in granular systems (47), (48), excipient homogeneity (49), visualization of tablets after drug release (50).…”

Investigating the Influence of HPMC K4M and Eudragit L 100-55 on Guanfacine-Loaded Extended-Release Tablets

“…In matrix systems, the active pharmaceutical ingredient (API) is homogeneously dispersed using one or more polymers, such as microcrystalline cellulose, sodium alginate, carbopol, etc. (11,12). Hydroxypropyl methyl cellulose (HPMC) is a type of hydrophilic polymer that is widely used in the preparation of polymer matrices to extend drug release.…”