A pinboard by
Amanpreet Kaur

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.


Dermatokinetics as an important tool to assess the bioavailability of drugs by topical nanocarriers.

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