Background The prolonged release of active pharmaceutical ingredients is widely used to achieve long lasting therapeutic effects and has the advantage that patients can take their medication less often and so possible risks of adverse effects are reduced. Most methods for retardation used in industrially manufactured dosage forms cannot be applied in the case of individual preparations manufactured in pharmacies. The addition of a gelling agent, such as hypromellose in capsule production, could serve as a promising possibility for small scale production.
Purpose To compare the dissolution characteristics of capsules containing 20 mg ketamine hydrochloride and either a mixture of lactose and hypromellose or lactose alone. As there is no clear recommendation for the optimal lactose–hypromellose ratio, one established formulation was investigated.
Material and methods Capsule composition: 20 mg ketamine hydrochloride, 85 mg lactose monohydrate and 200 mg hypromellose versus gelatine capsules filled with 20 mg ketamine hydrochloride and 330 mg lactose monohydrate. Placebo capsules with hypromellose and lactose and with lactose alone were used as a reference for quantification. Dissolution was simulated in an experimental setup with 200 mL 0.1 M hydrochloric acid with stirring at a controlled temperature of 37±1°C. Depending on the capsule type and its dissolution, velocity samples were taken at defined intervals. Quantification was performed by UV/VIS spectrophotometry at 268 nm. Dissolved placebo capsules containing lactose or lactose/hypromellose alone were used as reference. The method was validated regarding linearity, accuracy, precision and repeatability.
Results 5 dissolution tests on each capsule type were conducted. Capsules containing ketamine and lactose dissolved rapidly and liberated 100% ketamine within approximately 7 min. Those capsules containing hypromellose released only 70% active ingredient within 2 hours. Within this period the release was almost linear. At a calculated release rate of 0.12 mg/min, it can be estimated that in 150 min it will be fully released.
Conclusion Hypromellose had an marked effect on the liberation characteristics of a gelatine capsule when used as an excipient. It swells in aqueous solutions and prolonged the liberation of ketamine out of the matrix and contributed to very a consistent release. Hypromellose is therefore a promising excipient for individual pharmaceutical preparations with prolonged release.
References and/or acknowledgements Pharm Eur 8.4 (2014).
Hunnius; 11 Auflage (2014), de Gruyter.
No conflict of interest
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