Kongnara Papangkorn

Influence of crystallite microstrain on surface complexes governing the metastable equilibrium solubility behavior of carbonated apatites.

This study was on the influence of the mineral phase crystallite microstrain (CM) on the nature of the surface complex (SC) governing the metastable equilibrium solubility (MES) behavior of carbonated apatites (CAPs) in aqueous acidic media (0.10 M acetate buffers, with and without fluoride, 0.50 M ionic strength maintained with NaCl). The MES behavior of a set of four CAPs (synthesized at 85 degrees C by a precipitation method) of increasing CM and therefore of increasing MES (CAP4 > CAP3 > CAP2 > CAP1) was quantified. The following were the findings. For CAP1 and CAP2, the SCs deduced were Ca10(PO4)6(OH)2 and Ca10(PO4)6F2 for the nonfluoride and the fluoride cases, respectively. For CAP3 and CAP4, the SCs deduced were Ca9.5(PO4)6OH or Ca9.5(HPO4)(PO4)5(OH)2 and NaCa9.5(PO4)6F2 for the nonfluoride and the fluoride cases, respectively. These results together with that from an earlier limited study show that the Ca/P ratio of the SC decreases from 1.67 to 1.58 to 1.50 with increasing CM of the CAPs; this relationship inversely correlates with the chemistry of maturation of aqueously precipitated defective apatites. Also the SCs do not appear to exist as a continuous series and only a few SCs may account for the MES behavior over a wide range of CAP preparations.

Passive and oxymetazoline-enhanced delivery with a lens device: pharmacokinetics and efficacy studies with rabbits.

PURPOSE The aims of this study were to assess the trans-scleral delivery of dexamethasone phosphate (DexP) with a prototype lens device and a formulation comprising a vasoconstrictor and to determine the efficacy of this delivery system in treating experimentally induced uveitis in a rabbit model. METHODS Passive trans-scleral delivery was performed on New Zealand white rabbits in vivo, using the lens device and a formulation of 0.034 M oxymetazoline (OMZ, the vasoconstrictor) and 0.5 M of dexamethasone sodium phosphate (DexNaP). Trans-scleral delivery of DexP without OMZ was the control. The amounts of DexP delivered into the eye and its distributions in the eye were determined by dissection of the eye and high-performance liquid chromatography assay in the pharmacokinetics study. The efficacy of the DexP delivery system in treating lipopolysaccharide-induced uveitis was also evaluated in the rabbit model in vivo. The effect of OMZ upon DexP delivery and its treatment efficacy was studied by comparing the DexP results with and without OMZ. RESULTS In the pharmacokinetics study, the amounts of DexP delivered into the eye using the lens system with OMZ were significantly higher than those without OMZ. The results in the efficacy study showed a better treatment outcome with OMZ to relieve the symptoms of endotoxin-induced uveitis in rabbits. CONCLUSIONS The potential of vasoconstrictors to enhance eye disease treatments in passive trans-scleral drug delivery was demonstrated. The higher DexP level in the eye and the improvement of the outcome in the efficacy study in the presence of the vasoconstrictor are consistent with the hypothesis that the vasoconstrictor enhances drug delivery by decreasing clearance.

Quantitative Determination of Lattice Fluoride Effects on the Solubility and Crystallinity of Carbonated Apatites with Incorporated Fluoride

The purpose of this study was to evaluate quantitatively the effects of fluoride on the solubility and crystallinity of carbonated apatites (CAPs) after its incorporation into the crystal lattice using the metastable equilibrium solubility (MES) distribution method. Fluoride-incorporated CAPs (F-CAPs) of two different carbonate levels (3 and 5%) and fluoride contents from 0 to 20,000 µg/g were synthesized. X-ray diffraction experiments and Rietveld analysis were conducted to obtain crystallite microstrain and unit cell parameters. Acetate buffer MES solution media were prepared at two solution fluoride concentrations (0.2 and 2.0 mg/l) and at two pHs (5.0 and 5.7). The unit cell a-axis values of the F-CAPs were found to decrease as the fluoride content increased, consistent with the fluoride being incorporated into the crystal lattice. The fluoride concentrations in the MES solution media were high enough to provide a ‘swamping’ effect such that the fluoride released from the F-CAPs during dissolution was minimal in changing the solution fluoride concentration. Employing the MES distribution superposition method, it was shown that the surface complex possessing the fluorapatite (FAP) stoichiometry [Ca10(PO4)6F2] accounted for the MES distribution behavior of all experiments. In addition, the mean pIFAP [the value of –log(aCa10aPO46aF2) calculated from the ionic activity product based on FAP stoichiometry of the MES dissolution media in which 50% of the F-CAPs had dissolved] correlated well with the crystallite microstrain parameters of the F-CAPs. The incorporated fluoride in the F-CAPs showed only modest effects on F-CAP crystallinity and solubility.

Chemometric evaluation of physicochemical properties of carbonated-apatitic preparations by Fourier transform infrared spectroscopy†

The purpose of this study was to develop a simple and quick method of evaluating the physicochemical properties of carbonated apatite preparations (CAP) as an index of the bioaffinity of implantable materials based on Fourier-transformed-infrared (IR) spectra by chemometrics. The wet-synthesized CAPs contained various levels of carbonate content (CO(3)), and were analyzed microstrain parameter (MS), crystallite size parameter (CP), specific surface area (Sw), CO(3), and solubility parameter (pK(HAP)) using by X-ray powder diffraction, nitrogen gas adsorption, IR, and UV absorption. The IR spectral results of CAPs suggested that the peak intensities of CAP reflected the physicochemical properties of the samples. The IR data sets were calculated to obtain calibration models evaluating the physicochemical properties of CAPs by a partial least squares regression analysis (PLS). As validation of the calibration model, physicochemical properties of CAP could be evaluated based on validation IR data sets of independent samples, and those values had sufficient accuracy. The regression vector of each calibration model suggested that the physicochemical properties of CAP, such as CO(3), Sw, MS, CP, and pK(HAP), were affected by phosphate, hydroxyl, and carbonate groups.

Novel Dexamethasone Sodium Phosphate Treatment (DSP-Visulex) for Non-Infectious Anterior Uveitis: A Randomized Phase I/II Clinical Trial

ABSTRACT Purpose: Frequent steroid drops represent a challenge in patient compliance. This study evaluated the safety and efficacy of 5 minute topical dexamethasone sodium phosphate-Visulex (DSP-Visulex) treatment regimen (two applications on the first week then weekly after) compared to daily prednisolone acetate 1% (PA) for noninfectious anterior uveitis. Materials and Methods: Forty-four patients were randomized to 8% DSP-Visulex with placebo eye drops (8% group, n = 14), 15% DSP-Visulex with placebo eye drops (15% group, n = 15), or Vehicle-Visulex with PA eye drops (PA group, n = 15). Patients received daily eye drops and Visulex treatments on days 1, 3, 8, and 15 with an optional treatment on day 22. Efficacy measures were change in anterior chamber cell (ACC) count from baseline and proportion of patients with zero ACC count at days 8, 15, and 29. Safety measures were adverse events (AEs), visual acuity, ocular symptoms, and intraocular pressure (IOP). Results: ACC resolution over time was similar among the three groups. The percentage of patients with clear ACC was 18%, 22%, and 15% on day 8; 27%, 56%, and 54% on day 15; and 90%, 88%, and 77% on day 29 for the 8%, 15%, and PA groups, respectively. The numbers of reported AEs were 10, 36, and 12 for the 8%, 15%, and PA groups, respectively. Ten patients among all groups experienced treatment-related AEs, which included headache, eye pain, corneal abrasion, conjunctival/corneal staining, conjunctivitis, visual acuity reduction, and keratitis all of which were resolved during the timeframe of patients’ participation in the study. IOP elevation was noted in the PA group throughout the study, whereas IOP elevation in the DSP-Visulex groups was observed at day 3 but not thereafter. Conclusions: The efficacy of the DSP-Visulex applications was comparable to the daily PA drops in the treatment of noninfectious anterior uveitis. Both 8% and 15% DSP-Visulex treatments were safe and well tolerated.