Preparation and Evaluation of Transdermal Film Containing Solid Lipid Nanoparticles of Loronoxicam

Lornoxicam is a member of the oxicam group of non-steroidal anti-inflammatory drugs (NSAID) with extremely potent anti-inflammatory and analgesic activity. It is widely used for the symptomatic treatment of pain and inflammation in patient with osteoarthritis and rheumatoid arthritis. Moreover, it showed great efficacy in various clinical trials in the management of pre-operative and post-operative pain associated with gynaecological, orthopedic, abdominal, and dental surgeries. However, Lornoxicam usefulness is limited due to its short half-life that ranges from 3 to 5 hours. Added to that, Lornoxicam shows a distinct pH dependent solubility characterized by very poor solubility in acidic condition present in the stomach. Hence, this study aims to formulate SLNs loaded transdermal film of Lornoxicam. Lornoxicam-loaded SLNs were prepared by the emulsification-solvent diffusion method using different quantities of lipids i.e. Glycerol monostearate (GMS) & steric acid. Tween 80 and span 20 were used as non-ionic surfactants. Tweens and spans are the popular non-ionic surfactants used as vesicles forming agent in the preparation of SLNs their effect on the drug entrapment, vesicle size and drug release profile was determined. A total of 12 batches of SLNs were prepared using varying ratio of (SMS), steric acid and non-ionic surfactants. Then obtained SLNs were formulated into transdermal film using solvent casting method and subjected to various evaluation studies. FT-IR study was carried out to check any possible interactions between the drug and excipients. Pure drug was mixed with 1:1 ratio of excipients and checked for interaction if any. The major FT-IR peaks of drug were retained in the FTIR physical mixtures. The study results revealed that no major interaction between the selected drug and excipients. To quantify the drug concentration in the in-vitro samples, UV spectrophotometric studies were selected. Pure drug was dissolved in phosphate buffer pH 6.8: methanol (50:50 ratio) and λ max was found to be 376 nm in same solvents. The standard solutions were prepared using phosphate buffer pH 6.8: methanol (50:50 ratio) as mobile phase. Standard curve obtained with slope value 0.999 was used for the estimation of unknown samples. Lornoxicam loaded solid lipid nanoparticles were prepared by emulsification-solvent diffusion method. The solid lipid nanoparticles were evaluated for particle size, zeta potential and polydispersity index. Lornioxicam SLNs loaded transdermal films were prepared by solvent casting method using HPMC 100M. The films were evaluated for drug content, thickness, weight uniformity, moisture content, % moisture uptake, and in-vitro drug release. Film formulation showed low moisture content and uniform thickness. The in-vitro drug release profile of transdermal film was carried out by membrane diffusion method using Franz diffusion cell. All batches of film formulations were able to sustain the drug release for a period of 24 hours. The average percentage of drug released from the optimized transdermal film after 24 hours showed the drug release from the film formulations was Higuchi diffusion controlled and release mechanism was Super case-II mechanism. Based on the results of entrapment efficiency and in-vitro drug release studies, formulation F4 was subjected to short term stability study for 3 months. Result showed that there was no change in appearance, drug content, and % CDR when stored at 25ºC/60% and 40ºC/75% RH. Hence, stable Lornoxicam loaded transdermal films, which sustained the release of drug for prolonged period, certainly help in the better treatment of inflammation. Such type formulations decrease number of application of drugs and hence improve patient compliance. ACHIEVEMENTS: • A new attempt of oral drug namely Lornioxicam was exploited in this work as a very effective in TDDS. • Transdermal film developed proved to be effective in the delivery of the selected NSAIDs drug in therapeutic concentrations for prolonged period of time. FUTURE SCOPE: • Further this study can be extended to animal study, in order to evaluate the In-vivo efficacy of drug