†These authors contributed equally to this work.
2. Faculty of Pharmacy, University Laval, Pavillon Ferdinand-Vandry, 1050 Avenue of Medicine, Quebec, Canada.
This research project consisted in developing a new formulation for the direct compression of senna –an intrinsically non-compressible material originating from the dried pods of a plant named Cassia acutifolia. The challenge of finding adequate excipients to compress senna was combined to the challenge of maintaining similar weight and appearance to that of the currently marketed senna tablets. These challenges stemmed from the fact that the current formulation is composed of 80% senna, which created significant limitation for introducing compressible excipients. To overcome these challenges, currently marketed senna tablets are generally manufactured through wet granulation prior to compression, a process that is rather laborious and costly. The water acts as a binder in the granulation process, which allows the tablets to maintain their strength and integrity. However, wetting, drying and testing the granules for assay involves considerable time, labor and machinery as compared to the direct compression process. In addition to cost savings, direct compression does not require water or heat in the process, which could potentially reduce hydrolysis and oxidation of the active principle and enhance product stability. The development of senna formulation for direct compression was conducted in six experimental designs, where batches of senna tablets were manufactured as per specific matrices and analyzed for hardness, friability, disintegration, appearance, average weight, moisture and assay, as the project progressed. The results were compared to defined specifications which were based on the currently marketed senna tablets. A new formulation was found in the sixth experimental design, where optimal levels of hydroxypropyl cellulose, hydroxyethyl cellulose, lactose and croscarmellose sodium were identified. Tablet properties emerging from this formulation met all defined specifications at the time of manufacture and also after one month, three months and six months accelerated stability conducted as per the International Conference on Harmonisation guidelines. In conclusion of this project, a successful formulation for the direct compression of senna was discovered through "Design of Experiments" and "Quality by Design" methodologies. Furthermore, this efficient approach could be used again to develop other formulation presenting similar challenges and could potentially accelerate product launch in prospective pharmaceutical markets.
Keywords: Development, formulation, direct compression, design of experiment, quality by design