Particle and Gel Characterization of Irinotecan-Loaded Double-Reverse Thermosensitive Hydrogel

The irinotecan-loaded double-reverse thermosensitive hydrogel (DRTH) is a dispersed system of irinotecan-loaded solid lipid nanoparticles (SLN) in a thermosensitive hydrogel. To optimise the particle and gel properties of DRTHs for rectal administration of irinotecan, SLNs and DRTHs were prepared with tricaprin, triethanolamine, Tween 80, and Span 20. Among the SLNs tested, an SLN composed of 1 g irinotecan, 0.5 g lipid mixture, and 0.5 g combined surfactant gave the highest entrapment efficiency and smallest particle size. A DRTH composed of (poloxamer 407/poloxamer 188/combined surfactant/SLN dispersion/H2O (10/15/17/4/54%)) showed easy administration, fast gelling, and strong gel-forming in the body

Effects of Polymers on the Drug Solubility and Dissolution Enhancement of Poorly Water-Soluble Rivaroxaban

The purpose of this study was to investigate the efficacy of hydrophilic polymers in a solid dispersion formulation in improving the solubility and dissolution rate of rivaroxaban (RXB), a poorly soluble drug. The developed solid dispersion consisted of two components, a drug and a polymer, and the drug was dispersed as amorphous particles in a polymer matrix using the spray drying method. Polymeric solid dispersions were evaluated using solubility tests, in vitro dissolution tests, powder X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and particle size distribution analysis. To maximize physical stability against crystallization and improve the solubility and dissolution of RXB, it is important to select the appropriate polymer type and the optimal ratio of the polymer to the drug. The optimized polyvinyl alcohol (PVA)-based (1/0.5, w/w) and gelatin-based (1/5, w/w) solid dispersion formulations showed 6.3 and 3.6 times higher drug solubilities than pure RXB powder, respectively, and the final dissolution rate was improved by approximately 1.5 times. Scanning electron microscopy and particle size distribution analyses confirmed that the gelatin-based solid dispersion was smaller and more spherical than the PVA-based solid dispersion, suggesting that the gelatin-based solid dispersion had a faster initial dissolution rate. Differential scanning calorimetry and powder X-ray diffraction analyses confirmed that RXB had successfully changed from a crystalline form to an amorphous form, contributing to the improvement in its solubility and dissolution rate. This study provides a strategy for selecting suitable polymers for the development of amorphous polymer solid dispersions that can overcome precipitation during dissolution and stabilization of the amorphous state. In addition, the selected polymer solid dispersion improved the drug solubility and dissolution rate of RXB, a poorly soluble drug, and may be used as a promising drug delivery system

Supplemental effect of coated refined fish oil on the performance of finishing pigs fed diets containing soybean-meal as a partial alternative to barley or wheat feed ingredient

A total of 195 finishing pigs with an average body weight of 78.65 0.09 kg were assigned to 1 of 3 dietary treatments in a 28 days trial. The designated nutritional diets were as follows: CON; TRT1- CON + 0.2% coated refined fish oil; TRT2- CON + 10% barley + 0.2% coated refined fish oil. The inclusion of coated refined fish oil with the barley-based diet significantly increased body weight, average daily gain, and feed conversion ratio of finishing pigs throughout the experimental period. At the end of the experiment, pigs fed coated refined fish oil with the barley-based diet showed a significant improvement on nutrient digestibility of dry matter and nitrogen. Moreover, gas emission of NH3 and H2S concentration were significantly reduced. Also, drip loss during days 5 and 7 was significantly decreased in meat quality analysis of pigs fed coated refined fish oil supplemented to a barley-based diet. Furthermore, dietary coated refined fish oil with barley-based diet had significantly increased fatty acid profile of belly meat and reduced belly fat. In summary, the inclusion of coated refined fish oil with barley diet positively impacts on growth performance and nutritional values of meat quality in finishing pigsThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Preparation and Characterization of Pazopanib Hydrochloride-Loaded Four-Component Self-Nanoemulsifying Drug Delivery Systems Preconcentrate for Enhanced Solubility and Dissolution

The aim of this study was to develop a four-component self-nanoemulsifying drug delivery system (FCS) to enhance the solubility and dissolution of pazopanib hydrochloride (PZH). In the solubility test, PZH showed a highly pH-dependent solubility (pH 1.2 > water >> pH 4.0 and pH 6.8) and was solubilized at 70 °C in the order Kollisolv PG (5.38%, w/w) > Kolliphor RH40 (0.49%) > Capmul MCM C10 (0.21%) and Capmul MCM C8 (0.19%), selected as the solubilizer, the surfactant, and the oils, respectively. In the characterization of the three-component SNEDDS (TCS) containing Kolliphor RH40/Capmul MCM C10, the particle size of dispersion was very small (95% at 120 min) at four different pHs with 1% polysorbate 80, whereas the raw PZH and Kollisolv PG solution showed a pH-dependent poor dissolution rate (about 40% at 120 min), specifically at pH 6.8 with 1% polysorbate 80. In conclusion, PZH-loaded FCS in this work demonstrated enhanced solubility and a consistent dissolution rate regardless of medium pH

Comparison of 1-Palmitoyl-2-Linoleoyl-3-Acetyl-Rac-Glycerol-Loaded Self-Emulsifying Granule and Solid Self-Nanoemulsifying Drug Delivery System: Powder Property, Dissolution and Oral Bioavailability

The main objective of this study was to compare the powder property, dissolution and bioavailability of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG)-loaded self-emulsifying granule system (SEGS) and solid self-nanoemulsifying drug delivery system (SNEDDS). Various SEGS formulations were prepared, and the effect of surfactant and binder on the drug solubility in them, leading to selecting sodium lauryl sulphate (SLS) and hydroxyl propyl methyl cellulose (HPMC). The SEGS and SNEDDS were prepared with PLAG/SLS/HPMC/calcium silicate/microcrystalline cellulose at the weight ratio of 1:0.25:0.1:0.5:3 employing the fluid bed granulation and spray-drying technique, respectively. Their powder properties were compared in terms of flow ability, emulsion droplet size, scanning electron microscopy, and powder X-ray diffraction. Furthermore, the solubility, dissolution, and oral bioavailability in rats of the SEGS were assessed in comparison with the SNEDDS. The SEGS and SNEDDS enhanced the solubility of the drug approximately 36- and 32-fold as compared with the drug alone; but they had no differences. The crystalline drug may exist in both the calcium silicate and microcrystalline cellulose (MCC) in the SEGS, but only in the calcium silicate in the SNEDDS. The SEGS had considerably improved the flow ability (Hausner ratio, 1.23 vs. 1.07; Carr index, 19.8 vs. 43.5%) and drug dissolution as compared with the SNEDDS. The SEGS and SNEDDS with double peak profiles, unlike the single peak of drug alone, showed a significantly higher plasma concentration and area under the curve (AUC), as compared with drug alone. Although they were not significantly different, the SEGS gave higher AUC than did the SNEDDS, suggesting its enhanced oral bioavailability of PLAG. Thus, the SEGS could be used as a powerful oral dosage form to improve the flow ability and oral bioavailability of PLAG, an oily drug

Improved Bioavailability and High Photostability of Methotrexate by Spray-Dried Surface-Attached Solid Dispersion with an Aqueous Medium

Low aqueous solubility and poor bioavailability are major concerns in the development of oral solid-dosage drug forms. In this study, we fabricated surface-attached solid dispersion (SASD) to enhance the solubility, bioavailability, and photostability of methotrexate (MTX), a highly lipophilic and photo-unstable drug. Several MTX-loaded SASD formulations were developed for spray-drying using water as the solvent, and were investigated for their aqueous solubility and dissolution kinetics. An optimized ternary SASD formulation composed of MTX/ sodium carboxymethyl cellulose (Na-CMC)/sodium lauryl sulfate (SLS) at 3/0.5/0.5 (w/w) had 31.78-fold and 1.88-fold higher solubility and dissolution, respectively, than MTX powder. For SASD, the in vivo pharmacokinetic parameters AUC and Cmax were 2.90- and 3.41-fold higher, respectively, than for the MTX powder. Solid-state characterizations by differential scanning calorimetry and X-ray diffraction revealed that MTX exists in its crystalline state within the spray-dried SASD. The MTX-loaded SASD formulation showed few physical changes with photostability testing. Overall, the results indicate that the spray-dried MTX-loaded SASD formulation without organic solvents enhances the solubility and oral bioavailability of MTX without a significant deterioration of its photochemical stability

Improved Bioavailability and High Photostability of Methotrexate by Spray-Dried Surface-Attached Solid Dispersion with an Aqueous Medium

Low aqueous solubility and poor bioavailability are major concerns in the development of oral solid-dosage drug forms. In this study, we fabricated surface-attached solid dispersion (SASD) to enhance the solubility, bioavailability, and photostability of methotrexate (MTX), a highly lipophilic and photo-unstable drug. Several MTX-loaded SASD formulations were developed for spray-drying using water as the solvent, and were investigated for their aqueous solubility and dissolution kinetics. An optimized ternary SASD formulation composed of MTX/ sodium carboxymethyl cellulose (Na-CMC)/sodium lauryl sulfate (SLS) at 3/0.5/0.5 (w/w) had 31.78-fold and 1.88-fold higher solubility and dissolution, respectively, than MTX powder. For SASD, the in vivo pharmacokinetic parameters AUC and Cmax were 2.90- and 3.41-fold higher, respectively, than for the MTX powder. Solid-state characterizations by differential scanning calorimetry and X-ray diffraction revealed that MTX exists in its crystalline state within the spray-dried SASD. The MTX-loaded SASD formulation showed few physical changes with photostability testing. Overall, the results indicate that the spray-dried MTX-loaded SASD formulation without organic solvents enhances the solubility and oral bioavailability of MTX without a significant deterioration of its photochemical stability

Effects of silicone-based gels containing allantoin, dexpanthenol and heparin on hypertrophic scarring in the rabbit ear model

Silicone-based formulations are extensively used for the management of hypertrophic scars. Although the exact mechanism of action is still unknown, it has been postulated that some occlusion and hydration of the stratum corneum with subsequent cytokine-mediated signaling from keratinocytes to dermal fibroblasts is involved in its antiscarring effects. In this study, the effectiveness of silicone-based gels containing allantoin, dexpanthenol, and heparin was evaluated for improving the healing of hypertrophic scars. It was found that silicone-based gels showed remarkable improvements in hypertrophic scar healing and low amounts of skin pigmentation in the rabbit ear model compared with the nontreated control or base alone. Furthermore, the histopathological and histomorphometrical profiles of three different formulations containing 1%, 5%, and 20% silicone contents exhibited marked or significant decreases in the scar elevation index, anterior skin and epithelial thicknesses, inflammatory cells, vessels, collagen disorganization, and fibroblasts compared with nontreated control hypertrophic scars. Therefore, these results indicate that silicone-based gels containing heparin, allantoin, and dexpanthenol could be promising formulations for the healing of hypertrophic scars