ABSTRACT
Single formulation based delivery of probiotic-drug combination is envisioned as a superior therapeutic delivery modality for the diseases like Crohn's diseases, ulceritive colitis and Recurrent Clostridium difficile-Associated Diarrhoea (RCDAD). Keeping this perspective in mind, here we have developed natural gum [using a combination of aqueous solution of xantham gum (X) and guar gum (G)] modified sunflower oil based emulsion gels for the delivery of probiotics-drugs combination. FT-IR analysis and fluorescence microscopy together confirmed the formation of oil-in-water type emulsion gel by physical gelation in presence of the physical gelator sorbitan monopalmitate (SM). Other studies (XRD, DSC, mechanical properties and disintegration study) revealed that the variation in relative proportion of the two gums has a sporadic but significant effect on the physico-chemical properties of the gel. Post storage viability of commercially used probiotic Lactobacillus plantarum 299v (Lp 299v) at different storage conditions (4°C, -20°C, -196°C) was found higher in the emulsion gels with respect to the control. Moreover, the gels were found suitable for sustained delivery of metronidazole (the lipophilic drug often used with Lp 299v). In conclusion, the natural gum modified emulsion gel may be used as a delivery system for the probiotic-drug combination.
Subject(s)
Drug Carriers/chemistry , Drug Delivery Systems/methods , Emulsions/chemistry , Galactans/chemistry , Gels/chemistry , Mannans/chemistry , Metronidazole/pharmacology , Plant Gums/chemistry , Polysaccharides, Bacterial/chemistry , Probiotics/pharmacology , Administration, Oral , Calorimetry, Differential Scanning , Drug Liberation , Microbial Viability/drug effects , Microscopy, Fluorescence , Models, Theoretical , Probiotics/administration & dosage , Spectroscopy, Fourier Transform Infrared , X-Ray DiffractionABSTRACT
Modulation of crystallization of stearic acid and its derivatives is important for tuning the properties of stearate oleogels. The present study delineates the crystallization of stearic acid in stearate oleogels in the presence of Span 60. Microarchitecture analysis revealed that stearic acid crystals in the oleogels changed its shape from plate-like structure to a branched architecture in the presence of Span 60. Consequently, a significant variation in the mobility of the solute molecules inside the oleogel (Fluorescence recovery after photobleaching studies, FRAP analysis) was observed. Thermal analysis (gelation kinetics and DSC) revealed shortening of nucleation induction time and secondary crystallization with an increase in the Span 60 concentration. Furthermore, isosolid diagram suggested better physical stability of the formulations at higher proportions of Span 60. XRD analysis indicated that there was a decrease in the crystal size and the crystallinity of the stearic acid crystals with an increase in Span 60 concentration in the Span 60 containing oleogels. However, crystal growth orientation was unidirectional and found unaltered with Span 60 concentration (Avarmi analysis using DSC data). The mechanical study indicated a composition-dependent variation in the viscoelastic properties (instantaneous [τ1 ], intermediate [τ2 ], and delayed [τ3 ] relaxation times) of the formulations. In conclusion, Span 60 can be used to alter the kinetics of the crystallization, crystal habit and crystal structure of stearic acid. This study provides a number of clues that could be used further for developing oleogel based formulation.