Development and Evaluation of Chronotherapeutic Drug Delivery System for the Management of Nocturnal Asthma

Purpose: To develop an oral capsule-based chronomodulated drug delivery system of salbutamol sulphate for the treatment of nocturnal asthma.
Methods: The basic design of the proposed dosage form entails an insoluble cross-linked capsule body filled with drug-loaded pellets sealed with hydrocolloid plug and a soluble capsule cap. Various hydrocolloid polymers, namely, hydroxypropyl methylcellulose, (HPMC), hydroxypropyl cellulose (HPC), sodium alginate, polyethylene oxide (PEO) and guar gum. were used to optimize the plug material in the delivery in order to modulate lag period To avoid gastric transit time variability, the entire system was coated with Eudragit S100/Eudragit L100 dispersion (4:1), an enteric polymer system that dissolves at pH 6.8.
Results: Time-specific pulsatile release with 4 h lag period was achieved with crosslinked insoluble gelatin capsule shells containing pellets prepared from Avicel PH 101/lactose (80: 10) and 3 % Acidisol as disintegrant. In vitro data indicate that the developed pulsatile system released almost 98 % of the drug shoertly after the predetermined lag time of 4 h.
Conclusion: The developed system is capable of releasing the drug after a 4-h lag period. However, in vivo studies need to be carried out to ascertain the effectiveness of the formulation.

Keywords
Time controlled, pH-controlled, Lag time, pulsed release, Hydrocolloid plug, Nocturnal asthma