Development and physicochemical evaluation of pharmacosomes of diclofenac

Abstract

Diclofenac is one of the most widely prescribed non-steroidal anti-inflammatory drugs (NSAIDs). Use of diclofenac is associated with two major limitations; first, rare, but serious and sometimes fatal, gastrointestinal (GI) side-effects, including ulceration, and hemorrhage, especially in the elderly (1, 2), and second, poor water solubility. Pharmacosomes are amphiphilic lipid vesicular systems that have shown their potential in improving the bioavailability of poorly water soluble as well as poorly lipophilic drugs. Diclofenac is a poorly water soluble drug and also causes gastrointestinal toxicity. To improve the water solublity of diclofenac, its pharmacosomes (phospholipid complex) have been prepared and evaluated for physicochemical analysis. Diclofenac was complexed with phosphatidylcholine (80 %) in equimolar ratio, in the presence of dichloromethane, by the conventional solvent evaporation technique. Pharmacosomes thus prepared were evaluated for drug solubility, drug content, surface morphology (by scanning electron microscopy), phase transition behaviour (by differential scanning calorimetry), crystallinity (by X-ray powder diffraction) and in vitro dissolution. Pharmacosomes of diclofenac were found to be irregular or disc shaped with rough surfaces in SEM. Drug content was found to be 96.2 ± 1.1 %. DSC thermograms and XRPD data confirmed the formation of the phospholipid complex. Water solubility of the prepared complex was found to be 22.1 mg mL -1 as compared to 10.5 mg mL -1 of diclofenac. This improvement in water solubility in prepared pharmacosomes may result in improved dissolution and lower gastrointestinal toxicity. Pharmacosomes showed 87.8 % while the free diclofenac acid showed a total of only 60.4 % drug release at the end of 10 h of dissolution study.

In Vitro-In Vivo Evaluation of Novel Co-spray Dried Rifampicin Phospholipid Lipospheres for Oral Delivery

“…There was a significant increase (p < 0.001) in the solubility of SDRPL (2:1), 360 ± 12 versus 110.05 ± 15 μg/ml, and SDRPL (1:1) 310.12 ± 20 versus 110.05 ± 15 μg/ml in comparison to RMP. This improvement in solubility can be attributed to the amorphous form of the SDRPL along with the solubilizing and surfactant effect of the phospholipid (27)(28)(29).…”

Diclofenac transdermal patch versus the sustained release tablet: A randomized clinical trial in rheumatoid arthritic patients

“…The topical or transdermal delivery of drugs to patients with RA is known to improve patient compliance with immediate and prolonged release of the drug [4][5][6]. The use of a single patch for the whole day is expected to be more patient friendly compared with frequent oral dosing of tablets.…”

“…Among the side effects reported, upper GI bleeding and GI toxicity are the most common [6]. Moreover, a high dosing frequency is desired for the majority of NSAIDs to provide prolonged relief from pain and inflammation.…”

Penetration Enhancement Effect of Turpentine Oil on Transdermal Film of Ketorolac

“…The conventional systemic delivery of NSAIDs is generally associated with the high incidence of serious gastrointestinal disturbances, more peripheral distribution (rather than the localized delivery for analgesia and anti-inflammatory effect) of drug leading to higher plasma levels and hence more adverse effects [4,5]. Therefore, transdermal drug delivery systems (TDDS) of NSAIDs are potential alternative measure of drug delivery with the added advantage of higher site specific delivery with low plasma concentration (leading to less adverse effects), circumventing of hepatic first pass effect, avoidance of gastric irritation/discomfort, no drug-drug interaction, prolonged drug release, controlled therapeutic responses and improved patient compliance [6][7][8].…”