A lyophilized surfactant-based rutin formulation with improved physical characteristics and dissolution for oral delivery.

Rutin (RUT) is a phytochemical flavonoid with numerous therapeutic potentials including antihypertension, cardioprotective, neuroprotective, and anti-cancer activities. Its clinical use is inhibited due to its poor aqueous solubility and permeability over oral administration. The present study aimed to overcome these problems through micellization and entrapment of RUT in solid dispersion (SD) using Poloxamer (POL) 407 and 188 as surfactant-based matrices. The RUT/SD formulations were prepared in serial drug loading concentrations in weight percentage to the total solid. The physical properties of the formed RUT/SD solids were characterized by several methods including polarizing microscopy, differential thermal analysis (DTA), X-ray diffractometry (XRD), scanning electron microscopy (SEM) and dissolution study. The dissolution test was performed using a paddle dissolution apparatus and samples were analyzed using UV spectrophotometry. Polarized microscope confirmed that the optical behaviors of the RUT/SD implied a formation of miscible RUT with POL matrices. The morphology of RUT/SDs varied from porous matrices with craters to smoother surfaces as a function of RUT concentrations. XRD and DTA data exhibited that RUT existed as partially amorphous. These data indicated that the higher concentration of RUT in the RUT/SD formulations, the higher amorphous proportion of the RUT in the solid state. Henceforth, this led to an increase in the percentage of dissolved RUT from the developed RUT/SD formulations at 94 to 100% compared to pure RUT at only < 35% within an hour. The present study disclosed the successful improvements in the physical characteristics of the RUT/SD formulations and their potencies for the future development for oral formulation.

Cloning, expression, and polymorphism at the 5'-flanking region of the GnRH gene and their association with laying traits in Muscovy duck (Cairina moschata).

Gonadotropin-releasing hormone (GnRH), a neuropeptide, plays a vital role in the hypothalamus-pituitary-gonadal (HPG) axis. In vertebrates, GnRH is crucial for the onset of sexual development and the entire reproductive process. The purpose of this study was to identify genetic factors associated with egg-laying traits of Muscovy ducks. The full-length cDNA (474 bp) of Muscovy duck GnRH was obtained and characterised. It encodes 92 amino acids containing a 1-amino acid signal peptide cleavage site. Phylogenetic analysis revealed that Muscovy duck GnRH has a close relationship with Anas platyrhynchos GnRH. GnRH showed significantly different expression profiles between 4 developmental periods in the hypothalamus, pituitary, and ovary. The expression of GnRH in the laying period (36 weeks) was higher than at other periods in the three tissues. GnRH was widely expressed in 12 examined tissues of nesting and laying Muscovy ducks. In the hypothalamus, pituitary and gonads, the expression of GnRH was higher than in other tissues. In laying Muscovy ducks, the expression of GnRH in the hypothalamus, pituitary, ovary, muscular stomach, pancreas, heart, duodenum and spleen was significantly higher than in nesting dusks. Differences were detected in the liver and glandular stomach between laying ducks and nesting ducks. Differences between the kidney and lung were not significant. In the pituitary, the GnRH and GnRH receptor (GnRHR) genes shared the same expression profiles during 4 time points. Both genes had the highest expression at 36 weeks of age. A mutation (g.206G > A) in the 5'-flanking region was associated with egg-laying performance. Individuals with genotype GG had better egg-laying performance than the individuals with genotype AA. GnRH may be used as a marker gene for laying performance in the Muscovy duck.

Cellulose- and Saccharide-Based Orally Dispersible Thin Films Transform the Solid States and Dissolution Characteristics of Poorly Soluble Curcumin.

This study aimed at developing and optimizing the orally dispersible thin film (ODTF) containing a plant-derived drug-curcumin (CUR). CUR belongs to a biopharmaceutical classification system (BCS) class IV compound that requires improving its water solubility and tissue permeability preceding formulation. An ODTF was applied to produce a solid dispersion matrix for CUR to resolve such solubility and permeability problems. The film-forming polymers used in the study were cellulose-based (hydroxypropyl methylcellulose/HPMC and carboxymethylcellulose/CMC) and saccharide-based maltodextrin (MDX). Poloxamer (POL) was also employed as surfactant and solubilizer. The solvent casting technique was applied to produce the films. The ethanolic solution of CUR was mixed with an aqueous solution of POLs and then incorporated into different film-forming polymers prior to casting. The processing of the CUR with POL solution was intended to aid in the even dispersion of the drug in the polymeric matrices and enhance the wettability of the films. The physical state and properties of the films were characterized in terms of their morphology, crystallinity of the drug, and phase miscibility of the mixtures. The dissolution profile of the films was also evaluated in terms of dissolution rate and dissolution efficiency. The obtained ODTF products were smooth and flat-surfaced. Physical characterization also indicated that the CUR was homogeneously dispersed in the ODTFs and no longer existed as crystalline material as revealed by X-ray diffraction (XRD). The CUR was also not phase-separated from the films as disclosed by differential scanning calorimetry (DSC). Such dispersion was achieved through the solubilizing effect of POLs and compact polymeric film matrices that prevented the CUR from recrystallization. Furthermore, the ODTFs also improved the dissolution of CUR by 3.2-fold higher than the raw CUR. Overall, cellulose-based films had favorable physical properties compared with saccharide-based films.

Curcumin micelles entrapped in eudragit S-100 matrix: a synergistic strategy for enhanced oral delivery.

BACKGROUND: Therapeutic activities of curcumin (CUR) via oral administration are hampered by the lack of bioavailability due to its poor water solubility and rapid degradation in GI tract. MATERIALS & METHODS: This preliminary study developed CUR micelle-eudragit S100 (EUD) dry powder (CM-EDP) spray-dried formulations. Poloxamer 407 was used as a micelle-forming agent and EUD as an entrapping matrix for protection over hydrolysis and enzymes in the GI tract. RESULTS: The morphology of CM-EDP showed agglomeration with cratering on the surface of particles. Differential thermal analysis and x-ray diffractometry data exhibited evidence that CUR was converted into amorphous solid. An increased concentration of micelle-forming and dispersion matrix polymers resulted in a high fraction of drug being converted into the amorphous state. A significant increase in dissolution by 7-10 times was achieved compared with that of raw CUR. CONCLUSION: The present study disclosed the CM-EDP potency for future development of CUR oral formulation.

Analytical method for the determination of curcumin entrapped in polymeric micellar powder using HPLC.

OBJECTIVES: Curcumin belongs to the family of curcuminoids, natural polyphenolic compounds that possesses neuroprotective properties, anti inflammatory and anticancer. Its entrapment in the developed casein-based micellar powder (CMP) and poloxamer-based micellar powder (PMP) was to enhance the solubility and improve the bioavailability. Henceforth, the present study aimed to acquire an efficient analytical method for the curcumin analysis in polymeric micellar formulations. METHODS: A fast and specific HPLC method was developed for analyzing curcumin in two different micellar matrices using casein and poloxamer. The HPLC was equipped with a C18 column (250 × 4 mm, 5 µm) and diode array detector. A designated isocratic elution of curcumin was employed using mobile phase with a composition of water (1%, v/v acetic acid) and acetonitrile in a ratio of 50:50 v/v. The employed flow rate was 1.0 mL/min and the analyte was examined at 421 nm. RESULTS: An effective analysis in HPLC was successfully achieved by the predetermined HPLC condition. A good resolution of peaks at the employed flow rate was achieved. The linearity was excellent in two different range of concentrations, 2-20 and 10-50 µg/mL. The selectivity, accuracy and precision fulfilled the acceptable requirements. CONCLUSIONS: The developed method was practically effective to qualitatively identified curcumin. In addition, the assay also effectively quantified the amount of curcumin in the polymeric entrapping matrices which demonstrates that it has great potential to be used in natural compound analysis.

Characterization and Dissolution Study of Micellar Curcumin-Spray Dried Powder for Oral Delivery.

INTRODUCTION: Curcumin faces a major challenge in clinical use due to its poor aqueous solubility, which affects its bioavailability over oral use. The present study was carried out to overcome this problem. METHODS: An amorphous micellar curcumin-spray dried powder (MC-SDP) with self-assembled casein was prepared by the addition of sucrose as a protectant. The dry powder of curcumin-loaded micelles was obtained by a spray-drying technique in the presence of sucrose as a protectant. The MC-SDP in the form of dry powder was further developed into tablets to investigate the dissolution profile. The physical properties of preformed powder were characterized by differential thermal analysis (DTA), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Quantitative analysis in the form of solutions was analyzed by high-performance liquid chromatography (HPLC). RESULTS: The physical properties demonstrated that MC-SDP varies from dented to smoother surfaces as a function of sucrose. Furthermore, melting transitions of curcumin in the form of MC-SDP were broadened in all sample mixtures, as observed in the DTA thermogram. The XRD spectra showed that the sharp and very intense peaks of single curcumin crystalline structure no longer existed in all MC-SDP forms, indicating that the mixtures were amorphous. Moreover, a further dissolution study of MC-SDP showed a significant increase of drug dissolved with the presence of sucrose, where >80% of curcumin from MC-SDP was dissolved within 30 min. CONCLUSION: The study demonstrated the manufacture of micellar spray-dried powder that would contribute to the development of oral delivery of curcumin.