Category: Formulation and Quality
Purpose: Medicinal plants are progressively becoming an effective source for traditional and modern medicine. Approximately 80% of the international population regularly consume traditional medicine. For these reasons, the World Health Organization endorses countries to focus research on safe and effective ways to address several disorders employing traditional medicine as most of these resources are easily accessible.
Sceletium tortuosum belonging to the Mesembryanthemaceae family is one of the most promising medicinal plant species endemic to Southern Africa. It is traditionally a masticatory herbal medicine, which is widely recognised for its use in the treatment of major depression, anxiety, insomnia, obsessive-compulsive disorders, inflammation, bulimia nervosa, digestive problems, and analgesic effects against toothache and stomach pains. Recent studies showed that it is safe to use and patients present with minimal to no side effects. Four major alkaloids (mesembrenone, mesembrine, mesembranol and mesembrenol) were identified and are responsible for the pharmacological action, and therefore, several commercial products are available, including conventional tablets, capsules, teas, sprays, extracts and tinctures; as well as Elev 8® tablets containing 25 mg Zembrin®. However, no medicated chewing gum (MCG) containing S. tortuosum is commercially available yet.
A growing need exists to reinvent existing drugs into innovative drug delivery systems (DDSs) and extend or maintain product patents. MCG is mostly used internationally for its confectionary role, but more research are being conducted to utilise it as a DDS. Due to recent advances in directly compressible excipients for manufacture of MCGs, production are becoming easier and more cost-effective. CAFOSA Gum SAU has developed Health-in-Gum® (HIG), directly compressible gum-like substances that are said to be free flowing; and when compressed, result in compacts that are similar in appearance to pharmaceutical tablets. However, significantly limited literature is available regarding direct compression of HIG 01, 03 and 04 bases. Therefore, this study intended to evaluate the physical characteristics of these gum bases by means of the SeDeM Expert Diagram System and to develop a novel directly compressed MCG DDS containing S. tortuosum crude extract.
Methods: Various MCG formulations were prepared containing one of Cafosa®’s HIG-bases (i.e. HIG 01, 03 or 04), S. tortuosum crude extract (API), sweetener, flavouring agent and lubricant (0% or 0.5% magnesium stearate) using a full factorial design of experiments (Figure 1). The flow and compressibility properties of the API, HIG-bases and the formulations were analysed employing the SeDeM Expert Diagram System where twelve parameters were tested and SeDeM diagrams constructed (Figure 2).
Formulations were tableted by means of direct compression on a Korsch® single tablet press with a 12 mm diameter flat punch. Each MCG-unit was formulated in such a way as to contain a theoretical value of 6.38 mg API that is equivalent to 50 mg raw S. tortuosum plant material, which represents the estimated quantity to be chewed as a single dose by indigenous people. Subsequently, all MCG-units of the different formulations were evaluated in terms of mass variation, crushing strength, diameter, thickness, tensile strength, friability and pharmaceutical availability to establish the most acceptable MCG formulations.
Results: All HIG-bases depicted enhanced flowability compared to the API powder. Ultimately, the SeDeM Expert Diagram System (Figure 2) predicted that it will most likely be impossible to directly compress the API into acceptable MCG-units. Conversely, the HIG-bases adhered to all criteria set, thus indicating their suitability for direct compression. Considering all results obtained it was verified that HIG 03 will perform best when directly compressed, closely followed by HIG 01. It was furthermore projected that the HIG-bases would improve the compressibility factor of the API to an acceptable value. This expectation was verified as MCG formulations that were successfully manufactured, presented with compressibility values within an acceptable range (< 5).
Additionally, the inclusion of magnesium stearate in at least 0.5% w/w was essential to alter the most problematic property (i.e. stickiness) of the API. Both the SeDeM Expert Diagram System and evaluation of the physical properties indicated that formulation S0.5HIG01 is most suited for development of MCG-units by means of direct compression as it depicted the highest calculated SeDeM-values. Physical property results further specified that formulation S0.5HIG03 produced MCG-units that are more uniform in weight, harder and stronger compared to the other HIG-base powder formulations. Dissolution studies conducted according to the British Pharmacopoeia, utilising a specialised Chewing Gum Testing DRT-1 apparatus and artificial saliva, indicated that formulation S0.5HIG01 could be deemed most successful as it released mesembrine and mesembrenone alkaloid concentrations of 48.981% and 54.475%, respectively.
Conclusion: The SeDeM Expert Diagram System could be successfully applied to directly compressible MCG formulations. Furthermore, different MCG-units containing S. tortuosum crude extract with different base powders in their formulations were developed with the potential to be manufactured and implemented in the pharmaceutical industry; where HIG01 was estimated more effective.