Purpose: The efficacy of a pharmaceutical product depends on the active pharmaceutical ingredient (API) as well as the nature of the excipients included. Excipient properties and quality characteristics may have a significant influence on the API dissolution. We investigated the dissolution performance of 3 direct-compressed theophylline-excipient blends by characterizing drug release, swelling and erosion behavior of the tablets containing hydroxypropyl methylcellulose (HPMC) and microcrystalline cellulose.
The purpose was to assess the feasibility of whole-dosage form UV-Vis dissolution imaging as a tool for functional characterization of selected excipients, HPMC and microcrystalline cellulose, used in solid oral dosage forms.
Methods: The tablets (10 mm diameter) contained 20% (w/w) of theophylline anhydrate and 80% (w/w) of either Avicel (microcrystalline cellulose) or Methocel (HPMC) K15M or K100M (average tablet mass 256, 224 and 222 mg, respectively). Dissolution was investigated using a Sirius SDi2 (Sirius Analytical Ltd, Forest Row, UK) equipped with a USP IV type flow cell comprising an UV-Vis imaging detector. Dissolution experiments (n = 3) were conducted applying imaging at 300 or 255 and 520 nm in 0.01 M HCl using flow rates of 6.2 or 12.3 ml/min at 37 °C for 3 h. The dissolution was also assessed by downstream monitoring of the effluent using spectrophotometry using a photodiode array UV-Vis spectrophotometer (USB4000, Ocean Optics, Largo, FL, USA).
Results: Swelling and formation of a transparent gel layer was observed for the HPMC tablets by imaging at 520 nm; the average increase in tablet diameter after 3 h was 3 mm. Almost similar penetration of water and theophylline release rates were found for the two HPMC qualities. In contrast, for the microcrystalline cellulose tablets swelling was not observed, consistent with an erosion-based drug release process (Figure 1A). The release of theophylline was detected by UV imaging using wavelengths of 255 and 300 nm. However, due to the molar absorptivity of theophylline at 255 and 300 nm and turbulent flow patterns within the flow cell, UV imaging data were only used in a qualitative manner. Consequently, quantification of theophylline release was done using the downstream spectrophotometer. Figure 1B and C show a relatively high initial dissolution rate from the microcrystalline cellulose based tablets as compared to the HPMC tablets. A change in flow rate had only a slight effect on drug release rates for HPMC tables but a pronounced effect on microcrystalline cellulose tablets.
Conclusion: UV-Vis imaging qualitatively and quantitatively visualizes the swelling, erosion and dissolution processes. Initial functional characterization of tablets containing theophylline and the excipients HPMC and microcrystalline in terms of swelling and erosion using UV-Vis dissolution imaging was achieved. The results obtained suggest that UV-Vis dissolution imaging may be developed into a useful tool for investigation of drug-excipient interactions and, thus become an important aid in formulation development.
Zhuoxuan Li– University of Copenhagen
Yu Sun– University of Copenhagen
Daniel Bar-Shalom– University of Copenhagen
Huiling Mu– University of Copenhagen
Henrik Jensen– University of Copenhagen
Susan Larsen– University of Copenhagen