Development and Evaluation of Taste Masked Immediate Release Dosage Forms of Lornoxicam

Abstract

Lornoxicam (LXM) is a NSAID with better-tolerated alternative for the management of moderate to severe pain. It is having half life of 3-5 hours and shows complete absorption from GIT. The conventional formulations of LXM exhibits slow onset of action. This provokes a strong need to formulate immediate release dosage forms of LXM which shows faster disintegration or dissolution of drug in oral cavity or gastrointestinal tract. In present investigation, different immediate release dosage forms of LXM like fast disintegrating tablet (FDT), fast dissolving film (FDF), medicated chewing gum (MCG) and oral soft gel (OSG) were developed in view to improve drug release. Lornoxicam is in bitter taste and as this dosage forms are used in mouth cavity, taste masking was found very essential. FDT was selected as one of the approach for immediate release of LXM. Eudragit EPO was selected as taste masking polymer and LXM:Eudragit EPO mixture was prepared by mass extrusion technique. Preliminary trials indicated LXM:Eudragit EPO in a ratio of 1: 3 as optimized and thus, used further for development of FDT. Central composite design was used to optimize the concentration of Ac-di-sol (Superdisintegrant) and pharmaburst 500 (coprocessed excipient). All the prepared tablets were optimized and evaluated for different parameters and drug release was compared. FDT containing 4% w/w Ac-di-sol and 80% w/w pharmaburst 500 shown faster disintegration time of 8 seconds and 92% drug release in 20 minutes. Research shown high patient compliance for FDF and thus chosen as another approach, As Eudragit EPO masked taste of LXM, it was also used for taste masking of LXM in film. However, film properties were not satisfactory. Thus, ion exchange resin was used, But this also shown poor film properties. Thus, inclusion complexation using beta cyclodextrin was used. Inclusion complexation was done by kneading method using water as solvent for kneading and kneading time and molar ratio of drug to beta cyclodextrin was optimized. 32 factorial design was selected to optimize the concentration of PVA:Pullulan and PEG 400. FDF containing 40% w/w of PEG 400 and 10:90 ratio of PVA: Pullulan was considered as optimized as it gave 98% drug release in 0.1 N HCl in 20 minutes and strength and flexibility in acceptable range. MCG is also an emerging dosage form used in mouth cavity. To provide faster onset of action, with no choking effect, swallowing of only drug without its excipients and exploring another novel drug delivery system –medicated chewing gum was selected as another approach. Eudragit EPO masked LXM was used in MCG but release of drug was occurred in mouth on chewing. So Kyron T114 as weak cationic exchange resin was used for taste masking. Drug resin ratio, swelling time, stirring time, pH and temperature were optimized. LXM: Kyron T-114 in ratio of 1:2 was used with Health in gum as gum base and directly compressed. Trial batches were performed to optimize concentration of plasticizer, flavour, sweetener, compressibility and flowability enhancer to make the chewing gum palatable and directly compressible. Optimized MCG containing Health in gum as gum base, 1% w/w PEG 400, aerosil (0.5% w/w) as glidant , talc(2% w/w) as anti-adherant, magnesium stearate(1% w/w) as lubricant, aspartame(6% w/w) as sweetener and peppermint as flavour gave 89 % drug release in 20 minutes of chewing. Oral soft gel is highly preferred by paediatric and geriatric patient as it is soft and smooth so can be easily swallowed without water. They can be used as such or it can be taken with food items such as biscuits and breads. Oral soft gel (OSG) contains around 60% w/w sugar, thus separate technique for taste masking was not used. 32 factorial design was selected to optimize concentration of gellan gum and sodium citrate. The gels were evaluated for viscosity and rapid drug release. The optimized OSG containing 0.3% w/w gellan gum and sodium citrate was having viscosity 1212 cps and 89% drug release within 20 min. All the optimized formulations were found stable when subjected to stability study as per ICH guidelines. The drug release of optimized formulation of FDT, FDF, MCG & OSG of LXM were compared with conventional marketed formulation. Comparative dissolution profile of all optimized formulations exhibited faster drug release compared to conventional marketed formulation. However, selection of immediate release dosage form depends on age, disease conditions and patient compliance. Thus, present study proves that development of different immediate release dosage forms provides rapid onset of action and selected approach used in present study can be applied for other drugs.