Floating dosage forms to prolong gastro-retention--the characterisation of calcium alginate beads.

Floating calcium alginate beads, designed to improve drug bioavailability from oral preparations compared with that from many commercially available and modified release products, have been investigated as a possible gastro-retentive dosage form. A model drug, riboflavin, was also incorporated into the formula. The aims of the current work were (a) to obtain information regarding the structure, floating ability and changes that occurred when the dosage form was placed in aqueous media, (b) to investigate riboflavin release from the calcium alginate beads in physiologically relevant media prior to in vivo investigations. Physical properties of the calcium alginate beads were investigated. Using SEM and ESEM, externally the calcium alginate beads were spherical in shape, and internally, air filled cavities were present thereby enabling floatation of the beads. The calcium alginate beads remained buoyant for times in excess of 13h, and the density of the calcium alginate beads was <1.000gcm(-3). Riboflavin release from the calcium alginate beads showed that riboflavin release was slow in acidic media, whilst in more alkali media, riboflavin release was more rapid. The characterisation studies showed that the calcium alginate beads could be considered as a potential gastro-retentive dosage form.

Citric acid prolongs the gastro-retention of a floating dosage form and increases bioavailability of riboflavin in the fasted state.

A floating dosage form based on calcium alginate beads has been developed. Riboflavin, was selected as the model drug and successfully incorporated into calcium alginate beads. The aims of the current study were to: (a) assess the influence of prolonged gastro-retention on the bioavailability of riboflavin from freeze dried calcium alginate beads administered under varying conditions of food intake and (b) to investigate the potential of citric acid to delay the gastric emptying of the calcium alginate beads. Gamma scintigraphy was selected as the method to monitor the movement of the calcium alginate beads in vivo. Riboflavin concentrations in the urine were analysed by HPLC. Prolonged gastro-retention can be achieved, in the fasted state, when citric acid solution is used as an administering vehicle. However, prolonged gastro-retention is not achieved to the same extent when the gastric emptying times are compared to those obtained in the fed state. The bioavailability of riboflavin improved when calcium alginate beads were administered in the fasted state with citric acid solution, compared to the bioavailability obtained when the calcium alginate beads were administered in the absence of citric acid.

The use of citric acid to prolong the in vivo gastro-retention of a floating dosage form in the fasted state.

Gastro-retentive dosage forms have the potential to improve local therapy and decrease the variation in bioavailability that is observed with a number of commercially available immediate and modified release preparations. In this study, a dosage form has been developed, utilising freeze-dried calcium alginate beads, designed to float on the surface of the stomach contents thus prolonging the retention time. The aim of the study was to also assess the in vivo behaviour of the radio-labelled calcium alginate beads when they were administered under fasting conditions with either water or an aqueous solution of citric acid, a potential gut transit delaying substance. The study was performed in healthy male volunteers who swallowed the radio-labelled calcium alginate beads after a 10h overnight fast. Gamma scintigraphy was selected as the method to monitor the movement of the calcium alginate beads. The volunteers consumed no further food or drink until gastric emptying of the calcium alginate beads was complete. The results indicated that prolonged gastric retention was achieved when the dosage form was administered with the citric acid solution when compared to retention in the absence of citric acid. Citric acid, therefore, has the potential to delay the gastric emptying of the calcium alginate beads when administered to fasted volunteers.