Narubodee Phadoongsombut

Development and evaluation of self-microemulsifying liquid and pellet formulations of curcumin, and absorption studies in rats

This study describes the development and characterization of self-microemulsifying drug delivery systems (SMEDDS) in liquid and pellet forms that result in improved solubility, dissolution, and in vivo oral absorption of the poorly water-soluble compound curcumin. Solubility of curcumin was determined in various vehicles, including oils, surfactants and co-surfactants. Pseudo-ternary phase diagrams were constructed to identify the most efficient self-emulsification region. The optimized SMEDDS used for curcumin formulations in liquid and pellet forms contained 70% mixtures of two surfactants: Cremophor EL and Labrasol (1:1), and 30% mixtures of oil: Labrafac PG and Capryol 90 (1:1). The curcumin-SMEDDS in liquid and pellet formulations rapidly formed fine oil-in-water microemulsions, with particle size ranges of 25.8-28.8 nm and 29.6-32.8 nm, respectively. The in vitro rate and extent of release of curcumin from liquid SMEDDS and SMEDDS pellets was about 16-fold higher than that of unformulated curcumin. Plasma concentration-time profiles from pharmacokinetic studies in rats dosed with liquid and pelleted SMEDDS showed 14- and 10-fold increased absorption of curcumin, respectively, compared to the aqueous suspensions of curcumin. Curcumin-SMEDDS liquid and curcumin-SMEDDS pellets were found to be stable up to 6 months under intermediate and accelerated conditions. These studies demonstrate that the new self-microemulsifying systems in liquid and pellet forms are promising strategies for the formulation of poorly soluble lipophilic compounds with low oral bioavailability.

Liquid and solid self-microemulsifying drug delivery systems for improving the oral bioavailability of andrographolide from a crude extract of Andrographis paniculata.

The purpose of this study was to develop self-microemulsifying formulations of an Andrographis paniculata extract in liquid and pellet forms for an improved oral delivery of andrographolide. The optimized liquid self-microemulsifying drug delivery system (SMEDDS) was composed of A. paniculata extract (11.1%), Capryol 90 (40%), Cremophor RH 40 (40%) and Labrasol (8.9%). This liquid SMEDDS was further adsorbed onto colloidal silicon dioxide and microcrystalline cellulose, and converted to SMEDDS pellets by the extrusion/spheronization technique. The microemulsion droplet sizes of the liquid and pellet formulations after dilution with water were in the range of 23.4 and 30.3 nm. The in vitro release of andrographolide from the liquid SMEDDS and SMEDDS pellets was 97.64% (SD 1.97%) and 97.74% (SD 3.36%) within 15 min, respectively while the release from the initial extract was only 10%. The oral absorption of andrographolide was determined in rabbits. The C(max) value of andrographolide from the A. paniculata extract liquid SMEDDS and SMEDDS pellet formulations (equivalent to 17.5mg/kg of andrographolide) was 6-fold and 5-fold greater than the value from the initial extract in aqueous suspension (equivalent to 35 mg/kg of andrographolide), respectively. In addition, the AUC(0-12h) was increased 15-fold by the liquid SMEDDS and 13-fold by the SMEDDS pellets compared to the extract in aqueous suspension, respectively. The results clearly indicated that the liquid and solid SMEDDS could be effectively used to improve the dissolution and oral bioavailability that would also enable a reduction in the dose of the poorly water soluble A. paniculata extract.

Characterization of mefenamic acid-guaiacol ester: stability and transport across Caco-2 cell monolayers.

AbstractPurpose. Prodrug of non-steroidal anti-inflammatory drugs (NSAIDs) or NSAIDs linked with guaiacol have been reported to suppress gastrointestinal (GI) toxicity or induce GI protective effect. In this study, mefenamic-guaiacol ester was synthesized and its physicochemical properties, stability, and transport across Caco-2 monolayers were investigated. Methods. Synthesis of the ester was carried out using mefenamic acid, guaiacol, N, N′-dimethylaminopyridine, and N, N′dicyclohexylcarbodiimide. The hydrolysis of the ester was investigated in aqueous buffer solutions pH 1-12 as well as in Caco-2 homogenate, human plasma, and porcine liver esterase. Caco-2 cell monolayers were utilized for transport studies. Due to the high lipophilicity of the ester with a calculated logP of 6.15, bovine serum albumin (BSA, 4%) was included in the receiver compartment to obtain a good in vitro-in vivo correlation. Permeation of the ester was assessed with or without the exposure of cells to PMSF, an inhibitor of esterase. Results. The ester was stable at a wide pH range from 1-10. However, it was hydrolyzed by enzymes from porcine liver esterase and Caco-2 homogenate. With the PMSF exposure on the apical (AP) side and in the presence of 4% BSA on the basolateral (BL) side, the transported amount of the ester from AP-to-BL direction was 14.63% after 3 hr with a lag time of 23 min. The Papp for the ester was 4.72 × 10-6 cm s-1. Conclusion. The results from hydrolysis studies indicate that this ester is a prodrug. The Papp value suggests the moderate absorption characteristic of the compound. The accumulation of this highly lipophilic ester in Caco-2 cells is reduced in the presence of BSA.

Development of a rubber elongation factor, surface-imprinted polymer-quartz crystal microbalance sensor, for quantitative determination of Hev b1 rubber latex allergens present in natural rubber latex products.

Molecularly imprinted polymers (MIPs) for screening to detect rubber latex allergens (Hev b1) in natural rubber based products were designed as artificial recognition polymeric materials coated onto a quartz crystal microbalance (QCM). The polymers were prepared using a stamp imprinting procedure after mixing optimum amounts of methacrylic acid-vinylpyrrolidone-dihydroxyethylene bisacrylamide and Hev b1 latex allergen proteins, obtained from rubber gloves. QCM measurements showed that the resulting polymer layers after removal of the proteins used in their preparation could incorporate structures and features down to nanometer scale of protein templates into the imprinted polymer much better than a non-specific control polymer under controlled sensor conditions and an optimized polymerization process. This selective polymer but not the non-selective polymer clearly distinguished between the latex allergen Hev b1 and proteins such as lysozyme, ovalbumin and bovine serum albumin, with a selectivity factor of from 2 to 4, and the response of the rubber elongation factors by an astonishing factor of 12. The imprinted cavities recognized specific binding sites and could distinguish among related hevein latex allergenic proteins isolated from fresh natural rubber latex; Hev b1, Hev b2, and Hev b3 with a selectivity factor of from 4 to 6. The different QCM measurements obtained presumably reflected slightly different conformations and affinities to the MIP binding sites. The sensor layers selectively adsorbed Hev b1 within minutes in amounts ranging from 10 to 1500 μg L⁻¹ and with a detection limit of 1 μg L⁻¹. This work has demonstrated that this new sensor provides a fast and reliable response to natural rubber latex protein, even after being extracted from the matrix of rubber gloves.

Stability of Extemporaneous Norfloxacin Suspension

The stability of norfloxacin as extemporaneous suspensions compounded from two brands of film-coated tablets (formulas I and II) was studied. The vehicle consisted of tragacanth, saccharin sodium, sorbitol solution, glycerin, paraben concentrate, peppermint spirit BP, purified water, and syrup USP. The final concentration of norfloxacin in the suspensions was 20 mg/ml. Formulas I and II were chemically stable for 28 days when stored in amber glass bottles at ambient temperature; however, their physical characteristics were different.

Quantitative analysis of povidone-iodine thin films by X-ray photoelectron spectroscopy and their physicochemical properties

Abstract In this study, povidone-iodine (PVP-I) has been formulated as a topical spray to produce a thin film for the controlled release of I2. By means of experimental design, 27 formulations containing glycerol, ethanol, PEG 400, copovidone and HFA 134a as a propellant were prepared. The pH values of all formulations were in the range of 6-7. The viscosity was within the range of 11.9-85.9 mPa s. The surface tensions were 20.3 to 24.6 mN m-1 and the contact angles were between 19.3 and 38.7°. The assays for the iodine contents were within acceptable range (80-120 %). X-ray photoelectron spectroscopy analysis revealed the ionized form of iodine was much higher than the unionized form. The MIC and MBC values of the PVP-I sprays against Staphylococcus aureus, S. epidermidis and Pseudomonas aeruginosa were higher than that of commercial PVP-I solution. The cytotoxicity study confirmed that the PVP-I spray had lower toxic effects on keratinocytes and fibroblasts compared to the commercial PVP-I solution. The formulation containing 59 % ethanol, 18 % copovidone and 12 % PEG 400 showed good antibacterial activity.