Kampanart Huanbutta

Use of spray-dried chitosan acetate and ethylcellulose as compression coats for colonic drug delivery: effect of swelling on triggering in vitro drug release.

Spray-dried chitosan acetate (CSA) and ethylcellulose (EC) were used as new compression coats for 5-aminosalicylic acid tablets. Constrained axial or radial swelling of pure CSA and EC/CSA tablets in 0.1 N HCl (stage I), Tris-HCl, pH 6.8 (stage II), and acetate buffer, pH 5.0 (stage III), was investigated. Factors affecting in vitro drug release, i.e., % weight ratios of coating polymers, dip speeds of dissolution apparatus or pH of medium or colonic enzyme (beta-glucosidase) in stage III, and use of a super disintegrant in core tablets, were evaluated. Swollen CSA gel dissolved at lower pH and became less soluble at higher pH. The mechanism of swelling was Fickian diffusion fitting well into both Higuchis and Korsmeyer-Peppas models. EC:CSA, at 87.5:12.5% weight ratio, provided lag time rendering the tablets to reach stage III (simulated colonic fluid of patients), and the drug was released over 90% within 12 h. The system was a dual time- and pH-control due to the insolubility of EC suppressing water diffusion and the swelling of CSA in the stages I and II. The erosion of CSA gel in the stage III induced the disintegration of the coat resulting in rapid drug release. The lower dip speed and higher pH medium delayed the drug release, while a super disintegrant in the cores enhanced the drug release and no enzyme effect was observed.

Impact of salt form and molecular weight of chitosan on swelling and drug release from chitosan matrix tablets

Magnetic resonance imaging (MRI) and gravimetric techniques were used to assess swelling and erosion behaviors of hydrophilic matrix tablets made of chitosan. The impact of salt form, molecular weight (MW) and dissolution medium on swelling behavior and drug (theophylline) release was studied. The matrix tablets made of chitosan glycolate (CGY) showed the greatest swelling in both acid and neutral media, compared to chitosan aspartate, chitosan glutamate and chitosan lactate. MRI illustrated that swelling region of CGY in both media was not different in the first 100 min but glassy region (dry core) in 0.1N HCl was less than in pH 6.8 buffer. The tablets prepared from chitosan with high MW swelled greater than those of low MW. Moreover, CGY can delay drug release in the acid condition due to thick swollen gel and low erosion rate. Therefore, CGY may be suitably applied as sustained drug release polymer or enteric coating material.

Advanced technologies for assessment of polymer swelling and erosion behaviors in pharmaceutical aspect.

Clearly understanding of swelling kinetics and erosion behavior of polymer can reveal drug release mechanism and kinetics. Recently, swelling progression and mobility of water molecule inside polymers have been investigated by several technologies, including magnetic resonance imaging (MRI), X-ray microtomography (XμT), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), fluorescent, texture analyzer, and ultrasound techniques. Each technique offers its own advantages which suit to different study purposes. This review describes application of the advanced technologies to monitor swelling-erosion behaviors and also compares pros and cons of each technique. This may help the researchers to select the appropriate technique for their polymer.

Application of multiple stepwise spinning disk processing for the synthesis of poly(methyl acrylates) coated chitosan–diclofenac sodium nanoparticles for colonic drug delivery

The production of pharmaceutical nanoparticles by the spinning disk processing (SDP) technique has advantages in terms of its scalability and its capacity to produce readily tunable nanoparticles of narrow size distribution. In this study, we successfully developed a novel multiple stepwise SDP technique to develop aggregates of uniformly sized poly(methyl acrylates)-coated chitosan-diclofenac sodium nanocores (CS-PMA NPs) for colonic drug delivery. The processing conditions were optimized using the Box-Behnken design. SEM and TEM micrographs showed the optimized system to consist of 10 μm-sized agglomerates of CS-PMA NPs, the latter measuring 10nm in diameter. High drug entrapment of 88% was attained. Potential colon-targeted drug release from the CS-PMA NPs was demonstrated, with retardation of drug release in simulated gastrointestinal fluids and over 90% of the drug load released into simulated colonic fluid within 8 h. Drug uptake from CS-PMA NPs into Caco-2 cells was threefold higher than that from a control drug solution, with no apparent cytotoxicity observed at the NP doses administered. The collective data suggest that the SDP is a robust manufacturing method that can potentially be used to scale up the production of composite nanoparticulate colon-targeted drug delivery systems.

Design of porous Eudragit ® L beads for floating drug delivery by wax removal technique

Graphical Abstract The floating beads were fabricated by a novel wax removal technique. Metronidazole was successfully loaded into the Eudragit® L beads. Adding wax into the beads improved floating properties and drug release behavior. Release kinetics were revealed for better understanding of drug release mechanism.Unlabelled image

Use of seed gums from Tamarindus indica and Cassia fistula as controlled-release agents

Most seed gums have been widely used in oral and topical pharmaceutical formulations, cosmetics, and food products because of their hydrophilic properties. Gums from Tamariudus indica and Cassia fistula seeds were chemically modified by carboxymethylation to improve their functionalities. The objective of the present study was to characterize  and evaluate crude and carboxymethylated gums from T. indica and C. fistula seeds to achieve the controlled-release of diclofenac sodium (DS) in matrix tablet form. Both crude and carboxymethylated gums were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy. The results revealed that the gums were successfully modified by carboxymethylation and that the modified gums were amorphous in structure and had better flow properties. The carboxymethylated gums from both plant seeds did not exhibit cytotoxicity at concentrations lower than 0.5 mg/ml. All gum samples used as polymeric controlled-release agents were formulated into DS matrix tablets. Hardness and thickness tests were conducted as in-process tests. Drug content estimation and in vitro drug release studies were carried out to evaluate the matrix tablets. Increasing the concentration of gums increased compression time and hardness while it reduced the thickness. Furthermore, the results fitted well with the Korsmeyer–Peppas model. Moreover, the DS tablets were found to release the drug by super case II transport (relaxation). In summary, the carboxymethylated gum from T. indica and C. fistula seeds is an excellent, naturally sourced gum with high physicochemical and functional qualities, and can potentially be used in pharmaceutical applications as a disintegrant, diluent, and drug release-controlling agent.

Design and characterization of clindamycin-loaded nanofiber patches composed of polyvinyl alcohol and tamarind seed gum and fabricated by electrohydrodynamic atomization

In this study, we developed a polymeric nanofiber patch (PNP) for topical disease treatment using electrohydrodynamic atomization (EHDA). The nanofibers were prepared using various concentrations of polyvinyl alcohol (PVA) and tamarind seed gum and loaded with clindamycin HCl as a model drug. The precursor polymer solutions were sprayed using the EHDA technique; the EHDA processing parameters were optimized to obtain blank and drug-loaded PNPs. The skin adherence, translucence, and ventilation properties of the prepared PNPs indicated that they are appropriate for topical application. The conductivity of the polymer solution increased with increasing PVA and clindamycin concentrations, and increasing the PVA concentration enhanced the solution viscosity. Based on scanning electron microscopy analysis, the PVA concentration had a pronounced effect on the morphology of the sprayed product. Nanofibers were fabricated successfully when the solution PVA concentration was 10%, 13%, or 15% (w/v). The applied voltage significantly affected the diameters of the prepared nanofibers, and the minimum nanofiber diameter was 163.86 nm. Differential scanning calorimetry and X-ray diffraction analyses indicated that the model drug was dispersed in PVA in an amorphous form. The PNP prepared with a PVA:gum ratio of 9:1 absorbed water better than the PVA-only PNP and the PNP with a PVA:gum ratio of 9.5:0.5. Moreover, the PNPs loaded with clindamycin at concentrations of 1%–3% prohibited the growth of Staphylococcus aureus more effectively than clindamycin gel, a commercially available product.

Development and characterization of seed gums from Tamarindus indica and Cassia fistula as disintegrating agent for fast disintegrating Thai cordial tablet

Crude seed gum and their carboxymethyl derivatives from Tamarindus indica and Cassia fistula seeds were developed and characterized to apply as the pharmaceutical disintegrant in fast disintegrating Thai cordial tablet. The chemical structure of crude gum was chemically modified via carboxymethylation. Degree of substitution (DS) of carboxymethylated gums was determined. Carboxymethylated gums with minimum and maximum DS values were chosen for further application. IR absorption spectra of gum samples were observed to verify their chemical structure changes. In physical properties, the intrinsic viscosity and swelling property of all gum samples were evaluated. The results showed that carboxymethylated gums had higher intrinsic viscosity than those of crude gum. Moreover, they could swell and be soluble in cold water better than those of crude gums. In conclusion, the modified gums from both plants could provide higher hardness and be better used than that crude gums for fast disintegrating Thai cordial tablet. However, this is a preliminary assessment to expressing pharmaceutical application possibility of these gums as disintegrants, diluents and drug release controlling agents.