Formulation and development of floating multiple-unit minitablets of Nimodipine without using a gas-generating agent: in vitro and in vivo characterization

Abstract

Background: Floating drug delivery systems have been reported for different active pharmaceutical ingredients as single-unit tablets with gas-generating agents. In this present research, the formulation of floating multiple-unit minitablets of Nimodipine without using gas-generating agent was attempted with an objective of increased residence time, sustain-release and improved oral bioavailability. Solid dispersion with different ratios (1:0.5, 1:1, 1: 1.5, 1:2, 1:2.5) of drug with the lipophilic carrier such as Compritol ATO 888, Gelucire 43/01, G39/01 and Precirol ATO 05 was formulated using melt granulation technique. The adsorbent Sylysia 350 to lipophilic carrier is maintained at 1:1. The granules were compressed into minitablets weighing 15 mg and were filled into a '0' size capsule.Results: Differential scanning calorimetry study justified no interaction of the drug with excipients. The formulations which exhibited desirable flow property, floating lag time less than 1 min and floating time of 12 h were further characterized for various post-compression parameters. The optimized single-dose (capsule) of floating multiple-unit minitablets of Nimodipine consisting of 60 mg of drug, 120 mg of G43/01 and 120 mg of Sylysia 350 showed an average of floating lag time within 24.48 s, floating time of 14.32 h and sustained-release up to 12 h. Pharmacokinetic study of the optimized formulation (F9) showed nearly 2.5 times increase in area under the curve with increased residence time in comparison to aqueous suspension of Nimodipine. The stability study revealed no significant change in various parameters before and after storage.Conclusion: Hence, gelucire 43/01-based multiple-unit minitablets of Nimodipine can be considered a promising approach for sustaining the drug release with gastric retention for 12 h without using gas-generating agent.

Advancement in gastro retentive floating tablet: an updated review

“…The physical structure and chemical composition, crosslink density, crosslinking type, crosslinking solvent, network electrical charge, and physical appearance of different Carbopol® polymer grades affect their performance. For usage as controlled release polymers in matrix tablets, carbomers need polymer ratios between 3 and 30% [54].…”

A review on Advanced approaches and polymers used in gastroretentive drug delivery systems

“…When carbomers are utilised as controlled release polymers in matrix tablets, polymer ratios of 3 to 30 percent are necessary. Hydrogels derived from Carbopol and polycarbophil are generally extremely permeable to a variety of pharmacological compounds and can be designed to "swell," thereby releasing entrapped molecules via their network-like structures [24][25] . By adjusting the polymer concentration, the drug release can be fine-tuned.…”

In-Depth Study into Polymeric Materials in Low-Density Gastroretentive Formulations

“…Owing to their extreme hydrophobicity and low density, hydrophobic Gelucire are considered appropriate lipid carriers and drug release retardants in GRDDS such as multi-unit minitablets [ 113 ], lipid-based pellets [ 114 ] and floating granules [ 115 , 116 , 117 ]. Thus, sustained-release floating minitablets have been prepared using both G43/01 and G39/01 without the presence of gas generating agents [ 113 ]. They may also be part of lipid matrices in beads [ 114 , 118 ], play a role as floating assistant agents [ 119 ] and be of interest as a hydrophobic meltable binder [ 48 , 113 ].…”

“…Thus, sustained-release floating minitablets have been prepared using both G43/01 and G39/01 without the presence of gas generating agents [ 113 ]. They may also be part of lipid matrices in beads [ 114 , 118 ], play a role as floating assistant agents [ 119 ] and be of interest as a hydrophobic meltable binder [ 48 , 113 ].…”