Ph.D Research Scholar, Panjab University, Chandigarh
Topical treatment of arthritis pain
Diflunisal (DIF) is a salicylic acid derivative with high potency and longer duration of action. It is used orally for the management of pain and inflammation in rheumatoid arthritis. The oral administration leads to severe gastrointestinal side-effects. Hence, the present study was aimed at development and evaluation of solid lipid nanoparticle (SLN) based topical formulation of DIF for treatment of arthritis. Methods SLNs were prepared by hot microemulsion technique using Compritol ATO 888 as lipid, Tween 80 as surfactant and butanol as cosurfactant. Compritol 888 was heated 10 degrees above its melting point and DIF was added to it. An aqueous phase (surfactant: cosurfactant) was added to melted lipid at same temperature to form clear o/w microemulsion under stirring. Microemulsion was diluted with cold water (2-3°C) under continuous homogenization at 25,000 rpm for 10 min to obtain dispersion. The formula was optimized for selection of surfactant: cosurfactant mixture (Smix) in different ratios, Smix content and lipid content. The optimized SLNs were spherical in shape with an average particle size of 124±2.2 nm with PDI of 0.294±0.004. The entrapment efficiency was 76.78±2.273%. The formulations were found to be stable at 5±3°C, 25± 2°C and 40±2°C for a period of six months. The results of ex vivo permeation studies across mice skin depicted that SLNs showed 1.51 and 1.33 times higher cumulative amount permeated/area (109.99±0.008μg/cm2) and rate of permeation flux (6.30± 0.09 μg/cm2/h) respectively as compared to conventional cream. The skin retention from SLN gel was 11.74±0.155 μg/cm2 (2.19 times higher than conventional cream). The histopathological studies demonstrated the dermal safety of SLNs. The pharmacodynamic evaluation using xylene induced mice ear edema model depicted 1.41 times increase in percentage inhibition of edema after application of SLN gel as compared to conventional cream (Fig. 1). Similarly, in mice air pouch model, SLN gel showed 2.13, 2.86 times reduction in mean fluid volume and mean granuloma tissue weight respectively as compared to conventional cream. Also, the number of leukocytes/mm3 was drastically reduced with SLN gel. The SLN formulation depicted significantly higher permeation, skin retention and therapeutic efficacy at much reduced dose as compared to the oral dose. Hence, the developed SLNs based topical formulation of DIF could effectively be used to treat the local inflammation in joints of arthritic patients.
Abstract: Now-a-days, numerous nanocarrier-based drug products for topical applications are present in market and a huge number of similar products are being researched. To estimate the amount of drug delivery to skin, the scientists have now established techniques for separation of skin layers for the determination of drug concentrations. This forms the basis of pharmacokinetics of drug(s) in skin, i.e., dermatokinetics. However, dermatokinetic modeling of topical products is still a colossal challenge for scientists. Assessment of bioavailability helps in determination of safety and efficacy of topical formulations. As the methods used for determination of pharmacokinetics of oral and intravenous formulations are not useful for dermatokinetic assessment, various methods like tape stripping, microdialysis and vasoconstrictor assays are being used for dermatokinetic assessment.These methods are not only useful to determine the drug concentrations in various skin layers, but can also be used to correlate the toxicity effects of xenobiotics with skin layer concentrations. Despite advantages, there are some challenges in methodologies used for calculation of dermatokinetic parameters for furrows on skin and follicular drug penetration. Thereafter looking into all these issues, this article is an attempt to explore the usefulness and methodologies of dermatokinetics for nanocarrier-mediated topical delivery.
Pub.: 08 Mar '17, Pinned: 07 Jun '17
Abstract: Diflunisal (DIF) is non-steroidal anti-inflammatory drug used in the treatment of rheumatoid arthritis, osteoarthritis. The current engrossment was aimed at formulation and assessment of DIF-loaded solid lipid nanoparticles (SLNs) for topical/dermal application. SLNs formulated by hot homogenisation method based on microemulsification technique were spherical with a mean size of 124.0 ± 2.07 nm; PDI 0.294 ± 0.15. The cumulative amount permeated/area was 109.99 ± 0.008 μg/cm(2), along with permeation flux (6.30 ± 0.09 μg/cm(2)/h) and skin retention (11.74 ± 0.155 μg/cm(2)) across mice skin. The SLNs of DIF showed significant decrease in fluid volume, granuloma tissue weight, leukocyte count/mm(3) after application of SLN formulation in mice air pouch model. Similarly, in mice ear oedema and rat paw oedema model, there was 2.30 and 1.29 time increase in percentage inhibition of oedema after SLN formulation application, respectively, as compared with conventional cream. Hence, the SLNs of DIF may prove to be a potential nanocarrier to effectively treat the local inflammatory conditions associated with arthritis.
Pub.: 09 Aug '16, Pinned: 07 Jun '17
Abstract: Publication date: 10 November 2016 Source:Thermochimica Acta, Volume 643 Author(s): Amanpreet Kaur, Shishu Goindi, Om Prakash Katare Thermal analysis and quantitative characterization were done to evaluate the compatibility between DIF and various solid lipids explored like Compritol ATO 888, cetyl palmitate; CP, stearic acid; SA, glyceryl monostearate; GMS and hydrogenated castor oil. Till date, there are no reports on evaluation of DIF-lipid excipient compatibility. The techniques employed were differential scanning calorimetry; DSC, Fourier transform infrared spectroscopy; FTIR, optical microscopy, X-ray powder diffraction; XRPD studies and isothermal stress testing studies; IST. The results of DSC studies depicted displacement of DIF melting peak in binary mixtures suggesting some interaction between them. However, during IST studies less than 2% change in drug content was observed in all stressed samples of binary mixtures. Hence, the results demonstrated that all the selected solid lipids were compatible with DIF. Further, final SLN formulation was stable for 3 months. In conclusion, DSC and IST techniques were successfully employed to evaluate the DIF-lipid excipient compatibility. Graphical abstract
Pub.: 30 Sep '16, Pinned: 07 Jun '17