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Tetra-n-butyl ammonium chloride (TBAC) is known to form semiclathrate cages when dissolved in water. Melting points determined using differential scanning calorimetry (DSC) were used to create a phase diagram for the binary TBAC−H 2 O semiclathrate system from 0 to 8 molal TBAC at atmospheric pressure. This phase diagram shows the existence of TBAC semiclathrate cages with a congruent melting point at about 286.8 K at approximately 2 molal TBAC as well as the existence of a TBAC−H 2 O eutectic mixture of unknown composition but with fewer associated water molecules at higher concentrations of TBAC. Further, NaCl was added to this binary system to create ternary solutions of various ionic strength fractions of TBAC (Y TBAC ). The results of DSC scans were used to create a phase diagram which showed that there was no effect on the system if there was sufficient bulk water to dissolve the NaCl. However, if there was insufficient bulk water to dissolve the NaCl, then the water in the clathrate cages of the TBAC was disrupted creating both lower melting semiclathrates, with fewer water molecules within the cage, and a new TBAC−NaCl−H 2 O peritectic structure of unknown composition with an invariant melting point. Further, if NaCl was added to the binary system with no free, bulk water present (i.e., ≥ 2 molal TBAC), then this system additionally showed a new eutectic TBAC−NaCl−H 2 O structure of unknown composition with an invariant melting point.

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The objective of this study is to explore matrix-type microparticles, comprising a solid dispersion of drug with an ammonio methacrylate copolymer and ethylcellulose binary blend, for use in the controlled release of a poorly water-soluble drug, nifedipine. Microparticles consisting of an ethylcellulose N7 (N7) and Eudragit RL (RL) binary blend at different ratios were prepared using phase-separation methodology. The effects of matrix composition on microparticle properties were evaluated by polarized light microscopy, differential scanning calorimetry (DSC), FT-infrared and UV-visible spectroscopy, stability, and drug release studies. Study results indicate that the particle size distribution, particle morphology, and drug release rate from the microparticles were influenced by the ratio of RL to N7. Discrete spherical microparticles with a narrow size distribution and a controlled release profile were obtained when the ratio of RL to N7 was in the range from 1:1 to 2:1 w/w. Solid-state characterization and release kinetic studies on these microparticles confirmed that the nifedipine release from the microparticles followed the Baker and Lonsdale's matrix diffusion model (1974) for microspheres containing dissolved drug, and the nifedipine diffusion in the microparticle matrix was the rate-limiting step. As the ratio of RL to N7 was changed from 0:1 to 4:1 w/w, the effective drug diffusion coefficient in the micro-matrix increased from 5.8 x 10-10 to 8.6 x 10-9 (cm2/h). In addition, probably due to formation of a stable molecular dispersion promoted by hydrogen bonding between nifedipine and the polymers, no significant changes in the nifedipine physical form or release kinetics were observed after 1-year storage at ambient room temperature followed by 3-month accelerated stability at 40 degrees C/75% RH in a closed container.

Tetra-n-butyl ammonium chloride (TBAC) is known to form semiclathrate complexes with water. In this work, the melting points and latent heats of fusion of these semiclathrate structures were determined using Differential Scanning Calorimetry (DSC). A phase diagram was created for binary TBAC-H 2 O from 0 to 7.775 molal TBAC at atmospheric pressure. Below 2 molal TBAC, the semiclathrate is in equilibrium with free, bulk water. At approximately 2 molal TBAC a congruent melting point at 286.96 K is observed in this phase diagram. Beyond this composition, there is no free, bulk water present, and there are multiple forms of the TBAC-H 2 O semiclathrate complexes with varying amounts of water. Ternary TBAC-KCl-H 2 O systems were created by adding KCl to 1, 1.5, 2, 3, and 4 molal TBAC solutions to give ionic strength fractions of TBAC (Y TBAC ) from 0.25 to 1. It was found that the melting points of the TBAC-H 2 O semiclathrate were unaffected as long as there was a sufficient amount of free, bulk water at concentrations less than 2 molal TBAC. However, at greater concentrations, adding KCl disrupted the normal TBAC-H 2 O semiclathrate complex, and KCl was incorporated into new, TBAC-KCl-H 2 O complexes that melted at higher temperatures than previously reported for similar TBAC-NaCl-H 2 O complexes.