Thaned Pongjanyakul

Alginate-magnesium aluminum silicate films for buccal delivery of nicotine

Sodium alginate-magnesium aluminum silicate (SA-MAS) dispersions with nicotine (NCT) were prepared at different pHs and characterized for the particle size and zeta potential, NCT adsorbed by MAS, and flow behavior before film casting. The physicochemical properties, NCT content, in vitro bioadhesive property, and NCT release and permeation of the NCT-loaded SA-MAS films were investigated. This study showed that incorporation of NCT into the SA-MAS dispersions caused a change in particle size and flow behavior and that NCT could be adsorbed by MAS. The formation of protonated NCT at acidic and neutral pHs could interact with negatively charged MAS via an electrostatic force, resulting in the formation of NCT-MAS flocculates/complexes that could act as microreservoirs in the films. The NCT-loaded SA-MAS films prepared at pH 5 yielded the highest NCT content due to non-significant loss of NCT during drying. Moreover, pH of the preparation also affected the crystallinity and thermal properties of the films. The NCT release and permeation across the mucosal membrane of the films could be described using a matrix diffusion controlled mechanism. In addition, the NCT-loaded SA-MAS films also possessed a bioadhesive property for adhesion to the mucosal membrane. This finding suggests that the NCT-loaded SA-MAS films composed of numerous NCT-MAS complexes as microreservoirs demonstrated a strong potential for use as a buccal delivery system.

Chitosan-magnesium aluminum silicate nanocomposite films: physicochemical characterization and drug permeability.

Chitosan-magnesium aluminum silicate (CS-MAS) films were prepared and the effects of MAS content and heat treatment of the CS-MAS dispersion before film casting on the physicochemical and drug permeability properties of the films were investigated. CS could interact with MAS via electrostatic interaction and intermolecular hydrogen bonding mechanisms, resulting in nanocomposite formation, for which it was not necessary to apply the heat treatment on the composite dispersions. The nature of the exfoliated and intercalated nanocomposite films formed was depended on the MAS content added. The heat treatment on the composite dispersions caused an increase in tensile strength, but reduced %elongation of the CS-MAS nanocomposite films. The exfoliated nanocomposite films showed higher flexibility, water uptake, and drug permeability compared to the CS and intercalated CS-MAS nanocomposite films. At higher MAS content, the CS-MAS films prepared using heat treatment had a lower water uptake, resulting in lower drug permeability when compared with those prepared using non-heated dispersions. The permeation mechanism of non-electrolyte and negatively charged drugs across the CS-MAS nanocomposite films was predominantly controlled by diffusion in water-filled microchannels, whereas both adsorption onto MAS and diffusion processes occurred concurrently for the film permeation of positively charged drugs. The findings of this study suggest that CS-MAS nanocomposite films can be formed without heating of the composite dispersion before casting. CS-MAS nanocomposites showed strong potential to be used as a film former for coated tablets intended for modulating drug release.

Novel chitosan−magnesium aluminum silicate nanocomposite film coatings for modified-release tablets

Chitosan (CS), a positively charged polysaccharide, and magnesium aluminum silicate (MAS), a negatively charged clay with silicate layers, can electrostatically interact to form nanocomposite films. In this study, CS-MAS nanocomposite films were evaluated for use in tablet film coating. Effects of CS-MAS ratio and coating level on water uptake and drug release from the coated tablets were investigated. Surface and film matrix morphology of the coated film and the effect of enzymes in the simulated gastro-intestinal fluid on drug release were also examined. The results demonstrated that the CS-MAS coated tablets had a rough surface and a layered matrix film, whereas a smooth surface and dense matrix film on the CS coated tablets was found. However, the CS-MAS coated tablets provided fewer film defects than the CS coated tablets. Nanocomposite formation between CS and MAS could retard swelling and erosion of CS in the composite films in acidic medium. The higher MAS ratio of the CS-MAS coated tablets gave lower water uptake and slower drug release when compared with the CS coated tablets. Moreover, the CS-MAS films on the tablets presented good stability towards enzymatic degradation in simulated intestinal fluid. The release of drug from the CS-MAS coated tablets could be modulated by varying CS-MAS ratios and coating levels. Additionally, drug solubility also influenced drug release characteristics of the CS-MAS coated tablets. These findings suggest that the CS-MAS nanocomposites displays a strong potential for use in tablet film coating intended for modifying drug release from tablets.

Propranolol-magnesium aluminum silicate complex dispersions and particles: Characterization and factors influencing drug release

In this study, complexation of magnesium aluminum silicate (MAS) and propranolol HCl (PPN) in the form of dispersions and solid particles was investigated. PPN-MAS dispersions at different pHs were prepared and characterized. The physicochemical properties and in vitro drug release of the complexes were also examined. Incorporation of PPN into MAS dispersions at various pHs caused the formation of PPN-MAS flocculates with a different particle size, zeta potential and amount of PPN adsorbed. The PPN-MAS complexes prepared at various pHs were formed via cation exchange, hydrogen bonding and water bridging mechanisms, which were revealed by FTIR and solid-state (29)Si NMR spectroscopy. This led to the intercalation of PPN molecules into the silicate layers of MAS. In vitro drug release studies demonstrated that the kinetic release of PPN can be described using the particle diffusion controlled mechanism, suggesting that drug release was controlled by diffusion of the drug in aqueous channels in the particle matrix of the complexes. The PPN-MAS complexes provided a sustained-release of PPN after an initial burst release in acidic medium and pH 6.8 phosphate buffer when compared with the physical mixture and pure PPN powder. This was due to a slow diffusion of drug that was intercalated in the inside of the particle matrix. The preparation pH of the complexes did not influence the release of PPN; the important factors affecting drug release were particle size, percentage of drug loaded in the complexes and the type of release medium. This finding suggests that the PPN-MAS complexes obtained in this study are strong candidates for use as drug carriers in oral modified-release dosage forms.

Sodium alginate-magnesium aluminum silicate composite gels: characterization of flow behavior, microviscosity, and drug diffusivity.

The aims of the present study were to characterize the flow behavior and thixotropic properties of sodium alginate-magnesium aluminum silicate (SA-MAS) composite gels with various ratios of SA and MAS, and to investigate the drug diffusivity and microviscosity of the composite gels. Moreover, interaction of SA and MAS in the form of dry composite was examined by using Fourier Transform Infrared (FTIR), and a possible structure model of SA-MAS composite gel was illustrated. Incorporating MAS into the SA gels provided higher viscosity and changed the flow behavior from Newtonian to pseudoplastic with thixotropy. This was due to the formation of electrostatic force and inter-molecular hydrogen bonding between SA and MAS, leading to a denser matrix structure of the composite gels. Increasing the content of MAS decreased the drug diffusivity but increased the microviscosity of the composite gels. The denser matrix structure of the composite gels had a higher tortuosity, resulting in slower drug diffusion through water-filled channels in the gels. This finding suggested that incorporating MAS into the SA gels could improve the flow behavior and sustain drug release from the gels because of the formation of a matrix structure between SA and MAS in the gels.

Alginate–magnesium aluminum silicate films: Importance of alginate block structures

Sodium alginate-magnesium aluminum silicate (SA-MAS) composite dispersions were prepared and characterized for the flow behavior and morphology of their dispersed phase before casting. The high G block and high M block SA (GSA and MSA, respectively) were used. The physicochemical properties and permeabilities of the films were investigated using non-electrolyte and amine compounds in an acidic medium. The results showed that incorporation of MAS into the GSA and MSA dispersions gave identical flow behaviors and morphologies of MAS flocculates. FTIR spectroscopy revealed that the GSA and MSA presented similar molecular interactions with MAS in the films. However, the crystallinity of the GSA-MAS films was possibly higher than that of the MSA-MAS films. This indicated a higher density of matrix structure formed between GSA and MAS, resulting in lower water uptake in an acidic medium. Consequently, the permeability of the GSA-MAS films was lower than that of the MSA-MAS films. The diffusion and partition coefficients were directly related to the molecular weight of the non-electrolyte and amine compounds. This study suggested that transport of non-electrolyte compounds was predominantly controlled by diffusion in aqueous-filled microchannels, whereas both partition via adsorption onto MAS and diffusion in microchannels occurred concurrently for amine compounds.

Modification of quaternary polymethacrylate films using sodium alginate: Film characterization and drug permeability

The aims of this study were to investigate the molecular interaction of quaternary polymethacrylate (QPM) in aqueous-dispersion form with sodium alginate (SA) and to characterize the physicochemical properties, mechanical properties, and drug permeability of the QPM-SA films. The results demonstrated that QPM can interact with SA via electrostatic force, leading to the formation of flocculate particles in the dispersions. Transparent QPM-SA films were prepared using a casting/solvent evaporation method. The positively charged quaternary ammonium groups of QPM can interact with the negatively charged carboxyl groups of SA, which was observed using ATR-FTIR spectroscopy. This interaction caused a change of thermal properties, an increase in film strength, and a decrease in film tackiness. The puncture strength of the wet films in acidic media increased as the amount of SA was increased, but the flexibility of the films decreased. The wet films still presented good strength and flexibility in neutral pH when using 2.5-6.3%w/w SA because of their lower water uptake in such media. The incorporation of SA into QPM films was able to reduce drug permeability but increase drug diffusivity in acidic media. In contrast, the drug diffusivity decreased with the addition of a small amount of SA into the films when using a neutral medium. This phenomenon can be attributed to the effect of pH on the water uptake of the film and the ionization of the SA in the microenvironment of the films. These findings suggest that SA can modify the characteristics of QPM films, and QPM-SA films present a strong potential for application as a film coating material for modified-release tablets.

Influence of magnesium aluminium silicate on rheological, release and permeation characteristics of diclofenac sodium aqueous gels in-vitro.

The effect of magnesium aluminium silicate (MAS) on rheological, release and permeation characteristics of diclofenac sodium (DS) aqueous gels was investigated. DS aqueous gels were prepared using various gelling agents, such as 15% w/w poloxamer 407 (PM407), 1% w/w hydroxypropylmethylcellulose (HPMC), and 1% w/w high and low viscosity grades of sodium alginate (HV‐SA and LV‐SA, respectively). Different amounts of MAS (0.5, 1.0 and 1.5% w/w) were incorporated into the DS gels. Incorporation of MAS into the DS gels prepared using SA or PM407 caused a statistical increase in viscosity (P<0.05) and a shift from Newtonian flow to pseudoplastic flow with thixotropic property. The DS release rates of these composite gels were significantly decreased (P<0.05) when compared with the control gels. This was due to an interaction between MAS and PM407 or SA, and adsorption of DS onto MAS particles. Moreover, a longer lag time and no change in DS permeation flux were found when MAS was added to the gels. The findings suggest that the rheological characteristics of gels prepared using PM407 or SA could be improved by incorporating MAS. However, the use of MAS could retard the DS release and extend the lag time of DS permeation.

Acrylic Matrix Type Nicotine Transdermal Patches: In Vitro Evaluations and Batch-to-Batch Uniformity

Abstract Nicotine transdermal patches (NTPs) were fabricated using an acrylic pressure sensitive adhesive emulsion to form a transparent matrix film. An automated thin layer chromatography (TLC) plate scraper was used to control the thickness of the cast nicotine matrix film. The in vitro release behavior and permeation of nicotine across abdominal human epidermis (HE) from the NTPs was studied using United States Pharmacopeia (USP) dissolution apparatus 5 (paddle over disk) and modified Franz-diffusion cell, respectively. The release of nicotine from the NTPs showed a good linear correlation with the square root of time (R2>0.99). This indicated a matrix diffusion controlled-release mechanism. The surface morphology of the matrix of the NTP was uniform and nonporous before and after release, indicating that the dried adhesive nicotine matrix was a homogeneous single-phase film. Neither the nicotine content in the range 4.70–8.41% w/w nor the film thicknesses of the NTPs affected the apparent diffusion coefficient of nicotine in the acrylic matrix. A good relationship between the amount of nicotine permeated across the HE and the square root of time was also observed with R2>0.98. This study also showed that the NTPs provided a good delivery system with more than 65% of the nicotine delivery being controlled by the device. Moreover, the release of nicotine from six production batches met the criteria of USP 24. This finding presented a good potential of this method for upscaling to industrial manufacturing.

Permeation Studies Comparing Cobra Skin with Human Skin Using Nicotine Transdermal Patches

Cobra skin (Naja Naja Khaotia) was used as a barrier for an in vitro permeation study using nicotine. Fluxes of nicotine that permeated from Nicotinell ® through cobra skin (CS) taken from the head, body, and tail were 233.93 ± 16.08, 206.87 ± 19.00, and 211.26 ± 22.93 μg/cm2/hr1/2, respectively (n=6). This indicated no significant difference (p >. 05). Abdominal human epidermis (HE), obtained from cadavers, and the CS provided identical permeation kinetics for nicotine, which can be described by Mt = 4Mα=(Dt π L2)1/2. The mean flux of nicotine formulated as an acrylic transdermal patch that permeated through HE was 137.92 ± 67.79 μg/cm2/hr1/2 (4 specimens, n= 12), whereas that through CS was 180.13 ± 41.05 μg/cm2/hr1/2 (4 specimens, n= 15). The ratio of the fluxes of nicotine from formulated patches having three different nicotine contents using CS and HE was 1.22 to 1, respectively, for each of the patches irrespective of nicotine content. The coefficients of variation of the nicotine permeated were 22.79% and 49.15% for CS and HE, respectively, that is, a narrower variation of results was obtained with CS. This indicated that CS could be used for nicotine permeation studies.