Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate.

Purpose: The objective of this study was to exploit a novel methotrexate (MTX)-loaded solid self-microemulsifying drug delivery system (SMEDDS) with enhanced bioavailability and photostability. Materials and methods: The optimized liquid SMEDDS was composed of castor oil, Tween® 80, and Plurol® diisostearique at a voluminous ratio of 27:63:10. The solid SMEDDS was formulated by spray drying liquid SMEDDS with the solid carrier (calcium silicate). Particle size analyzer, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy experiments characterized the physiochemical properties of the MTX-loaded solid SMEDDS. These properties include a z-average diameter of emulsion around 127 nm and the amorphous form of the solid SMEDDS. Furthermore, their solubility, dissolution, and pharmacokinetics in Sprague-Dawley rats were analyzed in comparison with the MTX powder. Results: The final dissolution rate and required time for complete release of solid SMEDDS were 1.9-fold higher and 10 min shorter, respectively, than those of MTX powder. Pharmacokinetic analysis demonstrated 2.04- and 3.41-fold increments in AUC and Cmax, respectively in comparison to MTX powder. The AUC and Cmax were significantly increased in solid SMEDDS. Finally, the photostability studies revealed the substantially enhanced photostability of the MTX-loaded SMEDDS under the forced degradation and confirmatory conditions. Conclusion: This solid SMEDDS formulation could be an outstanding candidate for improving the oral bioavailability and photostability of MTX.

Development and evaluation of an oral fast disintegrating anti-allergic film using hot-melt extrusion technology.

The main objective of this novel study was to develop chlorpheniramine maleate orally disintegrating films (ODF) using hot-melt extrusion technology and evaluate the characteristics of the formulation using in vitro and in vivo methods. Modified starch with glycerol was used as a polymer matrix for melt extrusion. Sweetening and saliva-simulating agents were incorporated to improve palatability and lower the disintegration time of film formulations. A standard screw configuration was applied, and the last zone of the barrel was opened to discharge water vapors, which helped to manufacture non-sticky, clear, and uniform films. The film formulations demonstrated rapid disintegration times (6-11s) and more than 95% dissolution in 5min. In addition, the films had characteristic mechanical properties that were helpful in handling and storage. An animal model was employed to determine the taste masking of melt-extruded films. The lead film formulation was subjected to a human panel for evaluation of extent of taste masking and disintegration.

Comparison of solvent-wetted and kneaded l-sulpiride-loaded solid dispersions: Powder characterization and in vivo evaluation.

The purpose of this study was to compare the powder properties, solubility, dissolution and oral absorption of solvent-wetted (SWSD) and kneaded (KNSD) l-sulpiride-loaded solid dispersions. The SWSD and KNSD were prepared with silicon dioxide, sodium laurylsulfate and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) using a spray dryer and high shear mixer, respectively. Their powder properties, solubility, dissolution and oral absorption were assessed compared to l-sulpiride powder. The drug in SWSD was in the amorphous state; however, in KNSD, it existed in the crystalline state. The SWSD with a drug/sodium laurylsulphate/TPGS/silicon dioxide ratio of 5/1/2/12 gave the higher drug solubility and dissolution compared to the KNSD with the same composition. The oral absorption of drug in the SWSD was 1.4 fold higher than the KNSD and 3.0 fold higher than the l-sulpiride powder (p<0.05) owing to better solubility and reduced crystallinity. Furthermore, the SWSD at the half dose was bioequivalent of commercial l-sulpiride-loaded product in rats. Thus, the SWSD with more improved oral absorption would be recommended as an alternative for the l-sulpiride-loaded oral administration.

Mechanical properties and in vivo healing evaluation of a novel Centella asiatica-loaded hydrocolloid wound dressing.

To develop a novel sodium alginate based Centella asiatica (CA)-loaded hydrocolloid wound dressing (HCD) providing excellent mechanical properties and improved wound healing, numerous CA-loaded HCDs were prepared with various ingredients using the hot melting method. The effect of sodium alginate, styrene-isoprene-styrene copolymer (SIS) and petroleum hydrocarbon resin (PHR) on the mechanical properties of CA-loaded HCDs was investigated. The effect of disintegrants on swelling and drug release was assessed. Moreover, the in vivo wound healing potentials of the selected CA-loaded HCD in various wound models such as abrasion, excision and infection were evaluated in comparison with the commercial product. Polyisobutylene and SIS hardly affected the mechanical properties, but PHR improved the tensile strength and elongation at break. Disintegrants such as croscarmellose sodium, sodium starch glycolate and crospovidone improved the swelling ratio of the CA-loaded HCD. Furthermore, the CA-loaded HCD without croscarmellose sodium poorly released the drug, but that with 2% croscarmellose sodium showed about 27% drug release in 24h. In particular, the CA-loaded HCD composed of CA/polyisobutylene/SIS/PHR/liquid paraffin/sodium alginate/croscarmellose sodium at the weight ratio of 1/8/25/25/12/27/2 furnished excellent mechanical properties and drug release. As compared with the commercial product, it offered improved healing effects in excision, infection and abrasion type wounds in rats. Thus, this novel CA-loaded HCD could be a potential candidate for the treatment of various wounds.