Effect of a superdisintegrant on disintegration of orally disintegrating tablets determined by simulated wetting test and in vitrodisintegration test.

The disintegration time is critical for characterizing orally disintegrating tablets (ODTs), according to regulatory standards. The current study aimed to assess the effect of superdisintegrants such as sodium starch glycolate, croscarmellose sodium, and crospovidone on the disintegration of ODTs using simulated wetting and in vitro disintegration tests. The results showed that the wetting time of ODTs containing sodium starch glycolate and croscarmellose sodium was 17 - 21 s, but the wetting time of ODTs containing crospovidone was 9 - 12 s. In contrast, there was no significant difference in in vitro disintegration time among ODTs using different disintegrants (ca. 14 to 18 s) The quick wetting time of ODTs with crospovidone may be attributed to strong capillary characteristics of crospovidone. It is suggested that determining the disintegration time of ODTs just through simulated wetting test is insufficient and may lead to biases. As a result of the findings, it is recommended that an additional disintegration test, imitating saliva fluid absorption and tablet breaking, to provide a more precise evaluation of ODTs.

Development and optimization of Clinacanthus nutans liquid spray using a two-level full factorial design.

This study aimed to develop and optimize a topical Clinacanthus nutans liquid spray that dries quickly after spraying and has low stickiness. An experimental design was adopted to evaluate the effects of the amounts of polyvinylpyrrolidone (X1) and glycerol (X2) and the ratio of acetone:ethanol (X3) on the stickiness (Y1 ), solution viscosity (Y2), evaporation rate (Y3), and spray coverage radius (Y4) of the solution. Results revealed that all independent factors had a substantial effect on Y1 -Y3. In this model, the synergistic effect was uncommon. The optimized formulation consisted of X1 of 0.1%, X2 of 1.0%, and X3 of 59:41. The response values of Y1, Y2, Y3, and Y4 were 92.24 mN, 4.63 cP, 0.0959%, and 9.40 cm, respectively. The actual results were close to those predicted by the experimental design model. Therefore, the optimized topical spray formulation can be used in actual practice.

A burst drug release caused by imperfection of polymeric film-coated microparticles prepared by a fluidized bed coater.

The aim of this study was to investigate the drug release from microparticles coated with various polymeric films. Ibuprofen-loaded microparticles with diameter of 250 and 300 microm were prepared by a fluidized bed granulator. Five polymers were used as coating materials, i.e., ethylene vinyl acetate, ethyl cellulose, ethyl cellulose aqueous dispersion, polyethacrylate or Eudragit NE 30D, and carnauba wax. The coating was performed with a fluidized bed coater. Afterwards the coated microparticles were characterized in terms of particle size, morphology, and drug content. The drug dissolution was also investigated in pH 7.4 phosphate buffer. In our attempts for production of extended release ibuprofen microparticles coated with polymeric films, it was shown that the coating process had a significant effect on drug release. The undesired burst release of ibuprofen was observed in all film-coated microparticulate formulations, resulting from the imperfection of coating films.

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 Higuchi's 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.

Effect of chitosan salts and molecular weight on a nanoparticulate carrier for therapeutic protein.

The objective of this study was to investigate the potential of chitosan salts as a carrier in the preparation of protein-loaded nanoparticles. Glutamic and aspartic acids were used to prepare chitosan salts of 35, 100, and 800 KDa. Nanoparticles of chitosan base, chitosan glutamate, and chitosan aspartate were produced by ionotropic gelation with sodium tripolyphosphate (TPP). Bovine serum albumin (BSA) was applied as a model protein at loading concentrations ranging from 0.2 to 2 mg/mL. The size of the nanoparticles, as measured by photon correlation spectroscopy, was in the range of 195 to 3450 nm, depending on type and molecular weight of chitosan. Nanoparticles prepared with higher molecular weight chitosan showed larger sizes. The encapsulation was controlled by the competition of BSA in forming ionic cross-linking with chitosan and by the entrapment of BSA during the gelation process. Higher BSA encapsulation efficiency (EE) was obtained for nanoparticles prepared with chitosan salts compared to those prepared with the base. The higher EE was a result of a higher degree of ionization, causing more active sites to interact with BSA. In addition, a higher and faster release of BSA from the nanoparticles into pH 7.4 buffer medium was observed for nanoparticles of the chitosan salts than was observed for nanoparticles of the chitosan base. The higher and faster release was attributed to higher EE and lower entrapment of BSA within the matrix of the nanoparticle during the gelation process. The influence of molecular weight on the property of nanoparticles exhibited different effects. The difference was a result of different organic acids used to prepare nanoparticles leading to the difference in polymer conformation and viscosity of organic acid solution. Therefore, this study showed that the characteristics of chitosan nanoparticles loaded with a protein drug could be readily modulated by changing the salt form or the molecular weight of the chitosan carrier.

Characterization of chitosan acetate as a binder for sustained release tablets.

A chitosan derivative as an acetate salt was successfully prepared by using a spray drying technique. Physicochemical characteristics and micromeritic properties of spray-dried chitosan acetate (SD-CSA) were studied as well as drug-polymer and excipient-polymer interaction. SD-CSA was spherical agglomerates with rough surface and less than 75 microm in diameter. The salt was an amorphous solid with slight to moderate hygroscopicity. The results of Fourier transform infrared (FTIR) and solid-state (13)C NMR spectroscopy demonstrated the functional groups of an acetate salt in its molecular structure. DSC and TGA thermograms of SD-CSA as well as FTIR and NMR spectrum of the salt, heated at 120 degrees C for 12 h, revealed the evidence of the conversion of chitosan acetate molecular structure to N-acetylglucosamine at higher temperature. No interaction of SD-CSA with either drugs (salicylic acid and theophylline) or selected pharmaceutical excipients were observed in the study using DSC method. As a wet granulation binder, SD-CSA gave theophylline granules with good flowability (according to the value of angle of repose, Carr's index, and Hausner ratio) and an excellent compressibility profile comparable to a pharmaceutical binder, PVP K30. In vitro release study of theophylline from the tablets containing 3% w/w SD-CSA as a binder demonstrated sustained drug release in all media. Cumulative drug released in 0.1 N HCl, pH 6.8 phosphate buffer and distilled water was nearly 100% within 6, 16 and 24 h, respectively. It was suggested that the simple incorporation of spray-dried chitosan acetate as a tablet binder could give rise to controlled drug delivery systems exhibiting sustained drug release.

Composite film-coated tablets intended for colon-specific delivery of 5-aminosalicylic acid: using deesterified pectin.

Combinations of Eudragit RS and deesterified pectin, polygalacturonic acid (PGA), or its potassium and sodium salts, when applied as a film coat, has a potential value as a colon-specific delivery system. Dispersions of PGA in Eudragit RS were used as the film former for coating of 5-aminosalicylic acid (5-ASA) tablet cores. Drug release behavior was assessed, in vitro, under simulating conditions in term of pH and time to in vivo during their transit to the colon. Negligible drug release occurred during first 5 hr where the coated tablets were in the stomach and small intestine. After that, the pectinolytic enzymes were added into the pH 6.8 medium to simulate the in vivo condition where there is the digestion of bacteria in the colon. The release of 5-ASA from the coated tablets occurred linearly as a function of time. Drug release depended on the composition of the mixed film, as well as the ratio of Eudragit RS to PGA or its salts. The highest drug release from the coated tablets of about 40% was obtained when the ratio of Eudragit RS to potassium salt of PGA was 2.5 to 1. Drug release profiles seemed to conform to the mechanism involving the osmotically driven release and formation of channels in the film caused by dissolution of PGA salts. Channel formation was, in most cases, activated by the presence of pectinolytic enzymes, showing that the PGA in the mixed film was subjected to enzymic breakdown. In conclusion, PGA could be used as an additive in Eudragit RS films to control the release of colonic delivery system.

Studies on pectins as potential hydrogel matrices for controlled-release drug delivery.

Polymeric hydrogels are widely used as controlled-release matrix tablets. In the present study, we investigated high-methoxy pectins for their potential value in controlled-release matrix formulations. The effects of compression force, ratio of drug to pectin, and type of pectin on drug release from matrix tablets were also investigated. The results of the in vitro release studies show that the drug release from compressed matrix tablets prepared from pectin can be modified by changing the amount and the type of pectin in the matrix tablets. However, compression force did not significantly affect the drug release. The mechanisms controlling release rate were discussed with respect to drug diffusion through the polymer matrices, but may be more complex.

Effect of calcium concentration, hardening agent and drying condition on release characteristics of oral proteins from calcium pectinate gel beads.

Pectin has been investigated for its ability to produce solid calcium pectinate gel (CPG) beads containing bovine serum albumin (BSA). Several factors can influence the properties and release characteristics of the CPG beads. In this study, the effect of calcium concentration, hardening agent and drying condition on the encapsulation and release characteristics of BSA from the matrix gel beads made of calcium pectinate were studied. BSA release studies under conditions mimicking mouth to colon transit have shown that calcium pectinate protects the drug from being released completely in the physiological environment of the upper gastrointestinal tract, and is susceptible to the enzymatic action with consequent drug release. In addition, the release of BSA from CPG beads was strongly affected by calcium concentration and drying condition. However, the release was not particularly affected by the presence of hardening agent at the concentration of 1% or lower. Since the release of BSA as a model protein drug could be controlled by the regulation of the preparation conditions of CPG beads, the CPG beads may be used for a potential oral controlled release system for protein drugs.

Calcium pectinate gel beads for controlled release drug delivery: II. Effect of formulation and processing variables on drug release.

The effect of four formulation and processing variables, calcium concentration, drying condition, concentration of hardening agent and hardening time on the bead properties and the release characteristics of a model drug from calcium pectinate gel (CPG) beads were studied. A poorly soluble compound, indomethacin, was used as the model drug. The investigated variables affected the bead size, the entrapment efficiency and the release of indomethacin from CPG beads. Drug release was found to be a function of the formulation and processing variables. The slower drug release was achieved from the formulations with higher calcium concentration, higher concentration of hardening agent and longer hardening time. The drying condition, however, did not influence the drug release. The mechanism of indomethacin release from CPG beads followed the diffusion controlled model for an inert porous matrix. All drug release data fitted well to the Higuchi square root time expression.

Preliminary investigation of some polysaccharides as a carrier for cell entrapment.

Entrapment of cells within spheres of polysaccharide gel has become the most widely used technique for immobilizing living cells. Polysaccharide pectin, formed gel with calcium ions, was investigated as a precursor of spherical calcium polysaccharide gel beads. The type of pectin sample was found to be important in the formation of the beads. Partially deesterified pectin with a lower degree of esterification provided spherical beads and was chosen for immobilization of the yeast cells, Sacchararomyces cerevisiae, and compared to those with alginate. The effect of storage condition of the beads on the viability of the entrapped cells was also studied. After storage at 4 degreesC or -40 degreesC for 1 month, even lyophilization before storage, the beads with entrapped cells were sufficiently stable when compared to suspension of non-entrapped yeast cells.