Nicotine-magnesium aluminum silicate complexes processed by blending: Characterization for usage as drug carriers in mucoadhesive buccal discs.

Complexation of nicotine (NCT) and magnesium aluminum silicate (MAS) has been formed in the dispersions that required multiple preparation steps. In this study, physical blending was used to produce NCT-MAS complexes. NCT, a free-base liquid state form, was adsorbed onto the MAS granules, where the diffusion and intercalation of NCT molecules into the MAS silicate layers occurred. These processes required a minimum of the 7-d-resting period to reach NCT complete distribution. FTIR, XRD, and 29Si NMR suggest that NCT could interact with MAS via hydrogen bonding, water bridging, and ionic electrostatic force. The 12 % NCT-MAS complexes enabled a sustained release of NCT, after a 2-min burst, in pH 6 phosphate buffer through a particle diffusion-controlled mechanism. Buccal discs formulated with NCT-MAS complexes and sodium alginate (SA) as drug carriers and matrix former could control NCT released through drug diffusion and swelling-controlled mechanisms. NCT release and membrane permeation increased with increasing NCT-MAS complexes or decreasing SA concentration. All NCT-MAS-containing buccal discs exhibited mucoadhesive properties related to the swelling characteristics of SA and MAS. Conclusively, NCT-MAS complexes can be produced through an uncomplicated single-step blending process, and the complexes obtained presented a potential to serve as drug carriers in buccal matrix formulations.

Silicone matrices for controlled dexamethasone release: toward a better understanding of the underlying mass transport mechanisms.

Dexamethasone-loaded silicone matrices offer an interesting potential as innovative drug delivery systems, e.g. for the treatment of inner ear diseases or for pacemakers. Generally, very long drug release periods are targeted: several years/decades. This renders the development and optimization of novel drug products cumbersome: experimental feedback on the impact of the device design is obtained very slowly. A better understanding of the underlying mass transport mechanisms can help facilitating research in this field. A variety of silicone films were prepared in this study, loaded with amorphous or crystalline dexamethasone. Different polymorphic drug forms were investigated, the film thickness was altered and the drug optionally partially/completely exchanged by much more water-soluble dexamethasone 'phosphate'. Drug release studies in artificial perilymph, scanning electron microscopy, optical microscopy, differential scanning calorimetry, X-ray diffraction and Raman imaging were used to elucidate the physical states of the drugs and polymer, and of the systems' structure as well as dynamic changes thereof upon exposure to the release medium. Dexamethasone particles were initially homogeneously distributed throughout the systems. The hydrophobicity of the matrix former very much limits the amounts of water penetrating into the system, resulting in only partial drug dissolution. The mobile drug molecules diffuse out into the surrounding environment, due to concentration gradients. Interestingly, Raman imaging revealed that even very thin silicone layers (<20 µm) can effectively trap the drug for prolonged periods of time. The physical state of the drug (amorphous, crystalline) did not affect the resulting drug release kinetics to a noteworthy extent.

Sodium Alginate-Quaternary Polymethacrylate Composites: Characterization of Dispersions and Calcium Ion Cross-Linked Gel Beads.

The objective of this work was to examine the effect of quaternary polymethacrylate (QPM), a water-insoluble polymer with a positive charge, on the characteristics of the sodium alginate (SA) dispersions and the calcium alginate (CA) gel beads containing propranolol HCl (PPN). The SA-QPM composite dispersions presented the formation of flocculates with a negative charge due to the electrostatic interaction of both substances. The QPM addition did not affect the SA dispersions' Newtonian flow, but the composite dispersions' viscosity enhancement was found. The PPN-loaded CA-QPM gel beads had more spherical than the PPN-loaded CA gel beads. The incorporation of QPM caused a bigger particle size, higher drug entrapment efficiency, and greater particle strength of the gel beads. Despite the similar water uptake property, the PPN-loaded CA-QPM gel beads displayed lower burst release and slower drug release rate than the PPN-loaded CA gel beads. However, the drug release from the PPN-loaded CA-QPM gel beads involved drug diffusion and matrix swelling mechanisms. This study demonstrated that adding QPM into the SA dispersions leads to a viscosity synergism. The CA-QPM gel beads display a good potential for use as a bioactive compound delivery system.

Eudragit RL-based film coatings: How to minimize sticking and adjust drug release using MAS.

Polymeric film coatings based on quaternary polymethacrylates (QPMs, e.g. Eudragits®) are frequently used for controlled release applications. However, their considerable sticking tendency is a major drawback in practice. In this study, different amounts of magnesium aluminum silicate (MAS) were added to the film coatings in order to overcome this hurdle. MAS is negatively charged and can electrostatically interact with the positively charged QPM. Different types of tablet cores were coated with aqueous Eudragit® RL 30D dispersions, optionally containing varying amounts of MAS. Dynamic changes in the wet mass of the systems as well as drug release upon exposure to 0.1 M HCl and phosphate buffer pH 6.8 were monitored. Propranolol HCl, acetaminophen, and diclofenac sodium were used as cationic, nonionic and anionic model drugs. The tablets were optionally cured for 12 h at 45 or 60 °C. Importantly, the addition of MAS to aqueous Eudragit® RL 30D dispersion substantially reduced the films' stickiness and led to stable inner coating structures, even without curing. Desired drug release rates can be adjusted by varying the QPM:MAS ratio and coating level.

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 Fick's 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.

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 latter's 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.