Category: Formulation and Quality
Purpose: In recent years, more focus has been placed on creating both pharmaceutical and nutraceutical dosage forms that aim to provide the patient with a more enjoyable experience compared to traditional dosage forms. Gummy formulations provide a unique formulation that appeals to a wide range of consumers, from younger patients who don’t enjoy taking traditional dosage forms to geriatrics who are unable to take traditional dosage forms. Two common formulation challenges with gummies are masking the harsh taste of the bitter API as well as providing an animal-free product that can appeal to the entire population. Incorporating both IEX resins and carrageenan into a gummy provide a solution for both these challenges.
Methods: The resinates (i.e. drug-resin complexes) were synthesized using an aqueous solution of dextromethorphan hydrobromide @ room temperature. Amberlite™ IRP69 (DuPont) was added to the drug solution in the desired ratio. The wet cake was isolated, washed, and dried. The resinate loading was determined by using a calculator to obtain the theoretical loading, g of drug /g dry resinate, % resin capacity, and % efficiency of the process.
The control gummy formulation was prepared in a one-kilogram batch using a Vorwek Thermomix® TM5 set to temperature of 100°C. Gelcarin® GP-611 NF was dry blended with one-third of the total granulated sugar and dispersed into water while heating to 70°C. The remaining sugar, 42 DE Glucose Syrup and sodium citrate were added and cooked to a 78°Brix measurement, checked by refractometer. Color, flavor, and 50% citric acid solution were added to form the final gel mass. Gel mass was deposited into molds at greater than 90°C and allowed to cool to room temperature. When gummies were made with resin, drug or resinate in the gel mass, citric acid and sodium citrate were omitted.
Buccal dissolution experiments were run using a flow-through dissolution test apparatus that was developed and patented at DuPont. The concentration of drug in the simulated saliva is used as a proxy for taste, thus giving % taste masking efficacy data calculated by the difference in pure drug (Cmax) vs drug release from resin. (ref table#1).
Results: Drug loading of the resinate was 0.223g dextromethorphan/ g dry resinate. An equivalent dose of resinate equal to 30 mg of dextromethorphan hydrobromide was used for each formulation. Gummy integrity was excellent for all formulations under the conditions of the experiment as shown in figure #1. Using Cmax as the proxy for taste, the control, with a Cmax of 1998.6mg/L, was high representing high load of bitter drug in simulated saliva. Drug release from the formulation with resinate was extreemly low showing a 97% taste masking efficacy. Drug release from the in situ loading formulation was higher showing only 37% taste masking efficiency. With a slight adjustment of process optimization the efficiency would increase with increased contact time.