Srisagul Sungthongjeen

Effect of degree of esterification of pectin and calcium amount on drug release from pectin-based matrix tablets.

The aim of this work was to assess the effect of 2 formulation variables, the pectin type (with different degrees of esterification [DEs]) and the amount of calcium, on drug release from pectin-based matrix tablets. Pectin matrix tablets were prepared by blending indomethacin (a model drug), pectin powder, and various amounts of calcium acetate and then tableting by automatic hydraulic press machine. Differential scanning calorimetry, powder x-ray diffraction, and Fourier transformed-infrared spectroscopy studies of the compressed tablets revealed no drug-polymer interaction and the existence of drug with low crystallinity. The in-vitro release studies in phosphate buffer (United States Pharmacopeia) and tris buffer indicated that the lower the DE, the greater the time for 50% of drug release (T50). This finding is probably because of the increased binding capacity of pectin to calcium. However, when the calcium was excluded, the pectins with different DEs showed similar release pattern with insignificant difference of T50. When the amount of calcium acetate was increased from 0 to 12 mg/tablet, the drug release was significantly slower. However, a large amount of added calcium (ie, 24 mg/tablet) produced greater drug release because of the partial disintegration of tablets. The results were more pronounced in phosphate buffer, where the phosphate ions induced the precipitation of calcium phosphate. In conclusion, both pectin type and added calcium affect the drug release from the pectin-based matrix tablets.

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.

Development and in vitro evaluation of chitosan-Eudragit RS 30D composite wound dressings

The purpose of this research was to design and evaluate chitosan-based films intended for wound dressing application. Required properties for successful wound dressing, such as liquid uptake, vapor and oxygen penetration, bioadhesiveness, and film elasticity, were examined. Water uptake and vapor penetration of the films were determined gravimetrically, while oxygen penetration was determined by Winkler’s method. The bioadhesive properties were determined with an in-house pulley system instrument using a pig gut model. Film elasticity was determined with a stretch test using an Instron apparatus. The results showed that pure chitosan films exhibited relatively high liquid uptake and the adsorption tended to decrease with the addition of Eudragit RS 30D. Moisture vapor and oxygen were found to be able to penetrate through all film formulations in comparable amounts. The bioadhesiveness test tended to show lower bioadhesive properties with the addition of Eudragit RS 30D. The formulation containing only chitosan exhibited low elongation of the film at 2 N, but the film elasticity increased with the addition of Eudragit RS 30D. In conclusion, the addition of Eudragit RS 30D could improve a film’s mechanical properties but lower its bioadhesiveness.

Pectin-Based Bioadhesive Delivery of Carbenoxolone Sodium for Aphthous Ulcers in Oral Cavity

The objective of this study was to prepare and evaluate the pectin-based dosage form for buccal adhesion. Carbenoxolone sodium, which is used for the treatment of aphthous ulcers in oral cavity, was used as a model drug. The pectin buccal discs were prepared by direct compression. The water uptake and erosion of pectin disc increased progressively with the swelling time. The bioadhesion of dried pectin discs decreased when either the discs were hydrated or the buccal tissue was wet with a small volume of medium. The influencing factors such as pectin type, pectin to lactose ratio, and sweetener type on the formulations were investigated. The results demonstrated that buccal discs prepared from pectin with a high degree of esterification (DE) showed a weaker and more friable characteristic than that with low DE. Decreasing pectin to lactose ratio resulted in the high dissolution rate with low bioadhesive properties. Addition of sweetener in the formulations also affected the hardness, friability, and bioadhesive properties of the discs. The pectin discs containing sweetening agent showed a higher drug release than those without sweetener. The results suggested that pectin-based bioadhesive discs could be used to deliver carbenoxolone sodium in oral cavity.

Quaternary polymethacrylate–magnesium aluminum silicate films: Molecular interactions, mechanical properties and tackiness

The aim of this study was to investigate the impact of the addition of magnesium aluminum silicate (MAS), a natural clay, on the properties of polymeric films based on quaternary polymethacrylates (QPMs). Two commercially available aqueous QPM dispersions were studied: Eudragit(®) RS 30D and Eudragit(®) RL 30D (the dry copolymers containing 5 and 10% quaternary ammonium groups, respectively). The composite QPM-MAS films were prepared by casting. Importantly, QPM interacted with MAS and formed small flocculates prior to film formation. Continuous films were obtained up to MAS contents of 19% (referred to the QPM dry mass). ATR-FTIR and PXRD revealed that the positively charged quaternary ammonium groups of QPM interacted with negatively charged SiO(-) groups of MAS, creating nanocomposite materials. This interaction led to improved thermal stability of the composite films. The puncture strength and elongation at break of dry systems decreased with increasing MAS content. In contrast, the puncture strength of the wet QPM-MAS films (upon exposure to acidic or neutral media) increased with increasing MAS content. Furthermore, incorporation of MAS into QPM films significantly decreased the latters tackiness in the dry and wet state. These findings suggest that nanocomposite formation between QPM and MAS in the systems can enhance the strength of wet films and decrease their tackiness. Thus, MAS offers an interesting potential as novel anti-tacking agent for QPM coatings.

Manufacture of Ternary Solid Dispersions Composed of Nifedipine, Eudragit ® E and Adsorbent

The aim of this study was to manufacture the ternary solid dispersions composed of nifedipine, Eudragit® E and adsorbent. Dissolution enhancement of nifedipine was also investigated. The inert solid carriers were added in the mixtures of nifedipine and Eudragit® E at varying ratios. The physicochemical properties of ternary systems, compared to physical mixtures, were analyzed using powder x-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The dissolution of nifedipine from ternary systems was compared to the drug alone. The influence of drug:polymer: adsorbent ratio and type of adsorbent on the dissolution rate of the drug was also evaluated. The PXRD and DSC results of the systems with high amount of polymer showed that the drug was present in an amorphous form. On the other hand, the diffraction patterns and DSC thermograms of the physical mixtures revealed that to some extent the drug was present in a crystalline form. The results from this study demonstrated that an improvement in dissolution rate of nifedipine with Eudragit® E and adsorbents was obtained.

Quaternary polymethacrylate-magnesium aluminum silicate films: Water uptake kinetics and film permeability.

The aim of this study was to investigate the impact of the addition of different amounts of magnesium aluminum silicate (MAS) to polymeric films based on quaternary polymethacrylates (QPMs, here Eudragit RS and RL). MAS contains negatively charged SiO(-) groups, while QPM contains positively charged quaternary ammonium groups. The basic idea is to be able to provide desired water and drug permeability by simply varying the amount of added MAS. Thin, free films of varying composition were prepared by casting and exposed to 0.1M HCl and pH 6.8 phosphate buffer. The water uptake kinetics and water vapor permeability of the systems were determined gravimetrically. The transport of propranolol HCl, acetaminophen, methyl-, ethyl- and propylparaben across thin films was studied using side-by-side diffusion cells. A numerical solution of Ficks second law of diffusion was applied to determine the apparent compound diffusion coefficients, partition coefficients between the bulk fluids and the films as well as the apparent film permeability for these compounds. The addition of MAS resulted in denser inner film structures, at least partially due to ionic interactions between the positively charged quaternary ammonium groups and the negatively charged SiO(-) groups. This resulted in lower water uptake, reduced water vapor permeability and decreasing apparent compound diffusivities. In contrast, the affinity of the investigated drugs and parabens to the films substantially increased upon MAS addition. The obtained new knowledge can be helpful for the development of novel coating materials (based on QPM-MAS blends) for controlled-release dosage forms.

Impact of Anti-tacking Agents on Properties of Gas-Entrapped Membrane and Effervescent Floating Tablets

Tackiness caused by the gas-entrapped membrane (Eudragit®RL 30D) was usually observed during storage of the effervescent floating tablets, leading to failure in floatation and sustained release. In this work, common anti-tacking agents (glyceryl monostearate (GMS) and talc) were used to solve this tackiness problem. The impact of anti-tacking agent on the properties of free films and corresponding floating tablets was investigated. GMS was more effective than talc in reducing tackiness of the film. Addition and increasing amount of anti-tacking agents lowered the film mechanical strength, but the coating films were still strong and flexible enough to resist the generated gas pressure inside the floating tablet. Wettability and water vapor permeability of the film decreased with increasing level of anti-tacking agents as a result of their hydrophobicity. No interaction between anti-tacking agents and polymer was observed as confirmed by Fourier transform infrared spectroscopy, powder X-ray diffractometry, and differential scanning calorimetry studies. Increasing amount of anti-tacking agents decreased time to float and tended to retard drug release of the floating tablets. Floating properties and drug release were also influenced by type of anti-tacking agents. The obtained floating tablets still possessed good floating properties and controlled drug release even though anti-tacking agent had some effects. The results demonstrated that the tackiness problem of the floating tablets could be solved by incorporating anti-tacking agent into the gas-entrapped membrane.

An empirical model for dissolution profile and its application to floating dosage forms

A sum of two inverse Gaussian functions is proposed as a highly flexible empirical model for fitting of in vitro dissolution profiles. The model was applied to quantitatively describe theophylline release from effervescent multi-layer coated floating tablets containing different amounts of the anti-tacking agents talc or glyceryl monostearate. Model parameters were estimated by nonlinear regression (mixed-effects modeling). The estimated parameters were used to determine the mean dissolution time, as well as to reconstruct the time course of release rate for each formulation, whereby the fractional release rate can serve as a diagnostic tool for classification of dissolution processes. The approach allows quantification of dissolution behavior and could provide additional insights into the underlying processes.

Drug-Loaded Pectin Microparticles Prepared by Emulsion-Solvent Evaporation

The aim of this study was to develop the pectin-based microparticles by emulsion-solvent evaporation technique. The effects of concentration and type of pectin and addition of glutaraldehyde on size, size distribution, drug crystalline state and drug dissolution from microparticles were investigated. The results showed that a model drug, indomethacin, could be encapsulated in microparticles. Higher molecular weight of pectin caused a larger in size of microparticles than the lower one. A high degree of esterification is preferred to stabilize the pectin microparticles. The powder x-ray diffractograms showed that all microparticles led to amorphous products while their physical mixture still showed the crystalline state of drug. Drug dissolution from the microparticles containing indomethacin and pectin was increased, resulting from the formation of an amorphous solid dispersion. Addition of glutaraldehyde, however, resulted in slower drug dissolution, compared to the formulations without glutaraldehyde or drug alone.