Design and evaluation of pulsincap system containing nanosuspension of montelukast sodium for chronotherapy in asthma

In the present study, an attempt was made to prepare a pulsincap chronomodulated drug delivery system for the treatment of asthma and associated early morning allergy. Pulsincap capsule was prepared by sealing the drug nanosuspension inside the formaldehyde treated insoluble capsule bodies with a swellable and erodible guar gum plug. The drug, Montelukast sodium (MLS) nanosuspension was prepared by emulsion-solvent evaporation method using HPMC E15 and sodium lauryl sulphate (SLS). Nanosuspension formulations were optimized by using statistical Central composite design (CCD) for the required size and stability. The entire capsules were enteric coated using Cellulose acetate phthalate (CAP). This enteric coat prevents the drug release in the stomach, further the swellable hydrogel plug protect the nanosuspension to maintain the lag phase (5h) and facilitate its burst release in the colon. The length of this lag phase depends upon the concentration and quantity of the hydro gel plug. In order to simulate the GIT environment, the dissolution studies were performed using a sequential pH change method. DSC studies confirmed the absence of drug-excipient interactions. From the design space provided by the CCD, F14 and F15 formulations were considered as optimized. SEM studies were conducted for F14 formulation and this was filled in the Chronomodulated pulsincap systems (CMPs). These CMPs showed the drug release after 5h lag phase. Hence, when CMPs containing MLS nanosuspension is administered during bed time, it starts releasing the drug at the early morning hours to reduce asthma and associated early morning allergies like rhinitis and sneezing. Further, extensive in vivo studies are needed to be conducted to confirm the efficiency of these CMPs.