Enhancement of solubility, dissolution release profile and reduction in ulcerogenicity of piroxicam by inclusion complex with skimmed milk

Abstract

Context: Piroxicam (PXM), a non-steroidal anti-inflammatory drug which is poorly soluble in water and ulcerogenic. Milk has been used against the gastric disturbances caused by non-steroidal anti-inflammatory drugs. In this study, skimmed milk (SKM) is used as the carrier for inclusion complex (IC) due to its surface active agent and amino acid content. Purpose: To enhance the solubility, dissolution rate and prevent ulcerogenicity of PXM though IC with SKM. Methods: IC of PXM were prepared with SKM by solvent evaporation method using rota evaporator and were evaluated for solubility, dissolution, solid state characterization, drug excipient interaction, rat intestinal permeation, ulcerogenicity and histopathological studies. Results: Solubility of PXM was enhanced 2.5 times with IC. The dissolution release and amount of PXM permeated through rat small intestine was enhanced significantly with IC. Decreases in the gastric lesion index values of IC were observed than physical mixture (PM) and free PXM. The histopathological studies revealed significant reduction in ulceration in rat stomach after treatment with IC. Conclusion: It is concluded that SKM is a good carrier to prepare IC of PXM for oral administration.

Fabrication, In Vitro and In Vivo Evaluation of Non-Ordered Mesoporous Silica-Based Ternary Solid Dispersions for Enhanced Solubility of Flurbiprofen

“…The arbitrary scores (ASs) given to the ulcers were 0 for no ulcer/lesion, 0.5 for one or more ulcers of length <1 mm, 1 for ulcers/lesions of length 1–2 mm, and 2 for ulcers/lesions with length >2 mm. The arbitrary scores were multiplied with the number of lesions to determine the lesion index as follows [ 54 ]: Gastric lesion index (GLI) = AS × No. of ulcers/lesions …”

“…Microscopic Analysis All the stomachs of the animals were preserved in 20% v/v formalin buffer solution for histological analysis. Tissue sections of animals were observed under a microscope fitted with a 5 megapixel camera (Accuscope 3000, Commack, NY, USA) to determine the extent of ulceration and mucosal damage [54].…”

In Vitro Studies on Binary Mixture of Skimmed Milk and Urea as Solid Dispersion Carrier for Aceclofenac

“…The dispersions were kept in gyratory shaker at 25 ºC for 24 hrs following which the samples were filtered through Whatman filter paper(No. 1), suitably diluted withcorresponding medium and absorbances were measured spectrophotometrically at 270 and 273 nm respectively for double distilled water and phosphate buffer (pH 6.8) [32][33][34][35]. Solubilities of the formulations and corresponding % solubility enhancement with respect to the pure drug were calculated from the respective calibration curves by using the following formula(Equation 1).…”

The impact of digestion is essential to the understanding of milk as a drug delivery system for poorly water soluble drugs

“…The fat content in mammalian milk comprises over 95% triglycerides [1]. The recognition that these milk lipids can offer a solubilising environment for poorly water-soluble lipophilic drugs has led to a range of studies focusing on the solubility of drugs in milk [[2], [3], [4], [5], [6]] and in a limited number of studies the effect of milk on in vivo absorption and bioavailability [[7], [8], [9]]. The solubility of drugs in milk has been reported to be enhanced compared to that in aqueous media without fat present and in limited in vivo studies consequent increases in systemic exposure have been demonstrated.…”