(M1430-01-04) Formulation and In Vitro Evaluation of Carrageenan Based Gummies

Purpose: Improving patient compliance by reducing pill fatigue through innovative dosage forms has been a growing trend in both nutraceutical and pharmaceutical industries.  In addition, using plant-based excipients such as carrageenan to eliminate animal-based ingredients is another important market driver towards innovative dosage forms such as gummies and chewable softgel. Carrageenan is a family of carbohydrates extracted from seaweed (Irish moss) which has traditionally been used for numerous medical applications such as bronchitis dating back to the 1830s. Carrageenan has been also used in modern formulation development for softgel capsules and gummies. Changing to a new gummy formulation or switching from one gel former to another can present challenges and changing target properties. In this study, we investigated the influence of carrageenan grades on the properties of pharmaceutical gummy formulations. Caffeine was used as model drug.

Methods: Three grades of carrageenan from Kappa or Iota chemistry types (Kappa: Gelcarin^® GP 911 NF, Kappa: Gelcarin^® GP 611 NF, and Iota: Gelcarin^® GP 379 NF) with low to high viscosity were selected for manufacturing caffeine gummies targeting 250 mg dose. Table 1 shows the formulations. The gummies were prepared in a multipurpose cooking blender (Thermomix^®). Carrageenan was dry blended with one-third of the total sugar, dispersed into water, and heated at 70°C. The remaining sugar, glucose syrup, and sodium citrate were added and heated at 110°C for about 30 minutes until reaching a target sugar concentration (78°Brix) tested by a refractometer. Rest of the ingredients were then added, and each gel mass was deposited into silicon molds (gel temperature > 90°C). After cooling down at room temperature, the gummies properties were studied by analyzing the texture using a texture analyzer, disintegration time (DT) in four different media, and dissolution performance of fresh and one-year aged samples in de-ionized (DI) water.

Results: The combination of Gelcarin^® GP 911 and Gelcarin^® GP 379 did not form gummies, it resulted in a thin liquid gel. All other formulations formed firm to soft texture gummies as indicated by texture analyzer data shown in Fig 1.

The sample containing Gelcarin^® GP 911 produced firmer gummies than the sample containing Gelcarin^® GP 611. It is interesting to note that a combination of 2:1 Gelcarin® GP 611 /Gelcarin^® GP 379 resulted in firmer gummies than the sample containing Gelcarin^® GP 611 alone. The result suggested a synergy at a ratio of 2 to 1. The firmness of the gummies decreased with decreasing amount of Gelcarin^® 611 in the combinations of Gelcarin^® GP 611 /Gelcarin^® GP 379 from 2:1 to 1:1 and 1:2. Drug Release - Caffeine gummies F1 and F2 containing 1.8% Gelcarin® GP 911 and 1.8% Gelcarin^® GP 611, respectively, displayed a similar release regardless of differences in their texture. (Fig. 2) Combination of carrageenan grades slow down the release. It was noted F3 with the strongest gel and F5 with the weakest gel, had the slowest dissolution. It seems for caffeine release from gummies the gel strength is not a key factor, and chemistry of the carrageenan may be more impactful. A similar release was obtained from evaluating the gummies stored at room temperature for one year.

Conclusion: Five stable caffeine gummy formulations were manufactured using three different grades of carrageenan. Gelcarin® GP 911 and Gelcarin^® GP 611 formed gummies that were firm and not sticky. Gelcarin^® GP 911 gummies were firmer than Gelcarin^® GP 611 gummies. Dissolution of these two formulations also displayed a similar release. The combination of Gelcarin^® GP 911 and Gelcarin^® GP 379 only resulted in a thin liquid gel. The combination of Gelcarin^® GP 611 and Gelcarin^® GP 379 formed gummies, and the texture became less firm as the ratio of Gelcarin^® GP 379 increased in the formulation. Dissolution profile displayed a slower release of caffeine from the combination formulations of Gelcarin^® GP 611 and Gelcarin^® GP 379. The release of caffeine became slower with increasing the ratio of Gelcarin^® GP 379 in the formulations. Gummies dissolution did not change after one year storage at room temperature.


Figure 1. Texture properties of caffeine gummies


Figure 2. Comparative release profiles of freshly made caffeine gummies


Table 1. Formulations compositions for caffeine gummies