Hydrodynamically Balanced Capsules

Hydrodynamically Balanced Capsules

Apart from HBS tablets many investigators also formulated HBS capsules. The pharmacokinetics of the new drug delivery system named Madopar HBS was developed, which was characterized by lower and delayed plasma peak concentrations but a longer-lasting concentration of L-DOPA and benserazide than standard Madopar. Therefore, this new controlled release system reduced the clinical fluctuations occurring in parkinsonian patients with "wearing-off" and "on-off" phenomena The drug is released and absorbed over a period of 4-5 h, thus maintaining substantial plasma concentrations for 6-8 h after dosing. The presence or absence of food in the stomach has no effect on the absorption of L-DOPA from Madopar HBS, but administration of antacids reduces the bioavailability. Thus, Madopar HBS showed improvement in the clinical condition by about 86% on average as compared with standard Madopar
Khar  formulated sustained-release floating capsules containing salbutamol sulfate, using different combinations of hydrocolloids of natural and semi-synthetic origin. The floating capsule formulated showed a Higuchian release profile, while the marketed product released only about 80% of the total dose in the stipulated 12 h in the dissolution medium. In vivo x-ray studies of the abdomen indicated a residence time up to 8-9 h in the stomach greater than for the non-floating capsule.

A bilayer floating dosage unit composed of HPMC was formulated by Oth et al. to achieve local delivery of misoprostol (a prostaglandin E1 analog) at the gastric mucosa level. The use of a large capsule increases the GRT, as it impedes passage through the pylorus opening. GS studies revealed the average GRT was199 ± 69 min after a single meal (breakfast) and 618 ± 208 min after a succession of meals.

Hydrodynamically Balanced Systems with Gas-Generating Agents

Buoyancy in tablets and capsules could be achieved by incorporating hydrophilic matrix or by incorporation of some inorganic salts that generate gas when in contact with the gastrointestinal fluids.

Baumgartner et al developed the floating matrix tablets with HPMC and by incorporating gas-generating agent together with microcrystalline cellulose in the formulation. The tablet composition and mechanical strength were retained and the floating characteristics as well the drug-release pattern were maintained by properly optimizing the formulation. The floating time was optimized with floating lag time of approximately 30 s and the duration of floating was more than 8 h. Radiological evidence suggests that, the formulated tablets did not adhere to the stomach mucus and that the mean GRT was 4 h.

Ichikawa et al.developed an oral floating dosage system, which generated carbon dioxide gas. The system was composed of sustained release pills as seeds and double layers on the sustained release pills. The inner layer comprised an effervescent layer containing both sodium bicarbonate and tartaric acid separated by an inert layer. The outer layer was a swellable membrane layer containing mainly polyvinyl acetate and purified shellac. When the system was immersed in water, it formed swollen pills like balloons with a density much lower than 1.0 g/cm ³ . The reaction was due to carbon dioxide gas generated by neutralization in the effervescent layer with the diffusion of water through the swellable membrane layer. The buoyancy lag time was approximately 10 min and 80% remained floating over a period of 5 h irrespective of pH and viscosity of the test medium. The release rate of the drug from the system depends on the sustained release characteristics of the system. 

Minitablets formulated by Rouge et al achieved buoyancy either by the swelling of the excipient or by incorporation of the gas-generating agent sodium bicarbonate. The buoyancy of the minitablets containing atenolol was greatly improved by adding gas-generating agent sodium bicarbonate to the floating layer as well as by a wet granulation. Atenolol minitablets containing 7% sodium bicarbonate and coated with Eudragit NE30D:RS 70:30 yielded satisfactory results regarding buoyancy and drug release rate for 6 h. 

A bilayer floating tablet for gastric retention with cisapride as a model drug was developed by Wei et al  Sodium bicarbonate was added to the floating layer. The tablet when immersed in simulated gastric fluid (SGF) expanded and rose to the surface and eventually the drug was found to release gradually. The in vitro drug release of this type of bilayer dosage was controlled by the amount of HPMC in the drug loading layer. Generally, more the HPMC, slower the drugs release. As cisapride has greater solubility in SGF than simulated intestinal fluid (SIF), itsin vitro drug dissolution is faster as compared with SIF.

Frances et al. formulated 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 gastroretentive dosage form. They incorporated riboflavin as a model drug into the formula.

Reference:

http://www.sysrevpharm.org/article.asp?issn=0975-8453;year=2010;volume=1;issue=1;spage=33;epage=39;aulast=Sabale