Development and Evaluation of a Prototype Mobile Application for Intravenous Drug Dose Calculation in Overweight and Obese Thai Children: Precision Dosing in Practice.

Background: Medication dosing in overweight and obese children often involves complex weight-based calculations, leading to higher dosing errors, particularly with intravenous drugs. Currently, tools to aid in dosage calculations are lacking for these patients, especially in Thai population. Objective: This study aimed to develop a mobile application with the intent of utilizing it as a tool to enhance the efficiency and accuracy of dosing calculations required for obese and overweight Thai children. Methods: The performance of the application was assessed in 3 key aspects using a sample of 30 healthcare professionals. These key aspects included: 1) the accuracy of dosage calculations, assessed through pre- and posttests comparing manual calculations to app-based calculations using a 10-item questionnaire, 2) the time taken for calculations before and after app usage, 3) user satisfaction, which was measured through a questionnaire. Results: The integration of applications into the calculation demonstrated a significant improvement when compared to the manual calculation in both accuracy (6.10 vs 9.33 out of 10, P < .001) and efficiency (10.40 vs 8.53 minutes per 10 questions, P = .008). Also, the application elicited high levels of satisfaction among users, as reflected by an overall mean satisfaction score of 4.57 on a 5-point scale. Conclusion: The integration of this application to assist in dosage calculations for overweight and obese pediatric Thai patients has yielded favorable outcomes concerning accuracy, efficiency, and user satisfaction. Further development should be pursued within a larger cohort, with an emphasis on real-world implementation in clinical settings.

Solubility and Physical Stability Enhancement of Loratadine by Preparation of Co-Amorphous Solid Dispersion with Chlorpheniramine and Polyvinylpyrrolidone.

Loratadine (LRD), a non-sedating and slow-acting antihistamine, is often given in combination with short-onset chlorpheniramine maleate (CPM) to increase efficacy. However, LRD has poor water solubility resulting in low bioavailability. The aim of this study was to improve LRD solubility by preparing co-amorphous LRD-CPM. However, the obtained co-amorphous LRD-CPM recrystallized rapidly, and the solubility of LRD returned to a poor state again. Therefore, co-amorphous LRD-CPM solid dispersions using polyvinylpyrrolidone (PVP) as a carrier were prepared. The obtained solid dispersions were characterized using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR). The solubility, dissolution, and mechanism of drug release from the LRD-CPM/PVP co-amorphous solid dispersions were studied and compared with those of intact LRD, LRD/PVP solid dispersions, and co-amorphous LRD-CPM mixtures. The results from XRPD and DSC confirmed the amorphous form of LRD in the co-amorphous solid dispersions. The FTIR results indicated that there was no intermolecular interaction between LRD, CPM, and PVP. In conclusion, the obtained LRD-CPM/PVP co-amorphous solid dispersions can successfully increase the water solubility and dissolution of LRD and extend the amorphous state of LRD without recrystallization.

Compatibility and Physical Properties of Dexamethasone-Ondansetron Intravenous Admixture.

Purpose: This work aimed at evaluating the impact of different concentrations and final volumes on the compatibility and physical properties of dexamethasone-ondansetron intravenous (IV) admixture. Methods: The IV admixture of dexamethasone-ondansetron was prepared at different concentrations using normal saline solution as solvent. The final volume of the IV admixture was prepared at 50 and 100 ml. Turbidity was measured as an indicator of physical compatibility of the IV admixture of dexamethasone-ondansetron using UV-visible spectrophotometer and the pH of the IV admixture was measured on day 0, 7,14, and, 21 as an index of chemical stability. Also, the particle size and potential molecular interactions of the admixtures were determined using particle size analyzer and Fourier Transform infrared spectrometry analysis, respectively. Additionally, the effect of preservatives on the IV admixture was also evaluated. Results: Precipitation was observed for mixtures with amounts of dexamethasone and ondansetron exceeding 8 and 16 mg, respectively, in a final volume of 50 ml. For all mixtures with final volume of 100 ml, clear solutions void of any precipitates were observed. The pH of the solution had no effect on the precipitation of the dexamethasone-ondansetron during storage up to 21 days. Analyses of the precipitate formed revealed the presence of molecular interactions between dexamethasone and ondansetron. The benzyl alcohol used as a preservative affected the compatibility of the IV admixture compatibility. Conclusion: Thus, for the preparation of clear, physically compatible normal saline solutions of dexamethasone-ondansetron IV admixture, the maximum amounts of the respective drugs should not exceed 8 and 16 mg in total volume of 50 ml or 20 and 16 mg in a final volume of 100 ml.

The Binding of Alpinia galanga Oil and Its Nanoemulsion to Mammal GABAA Receptors Using Rat Cortical Membranes and an In Silico Modeling Platform.

The anesthetic effect of Alpinia galanga oil (AGO) has been reported. However, knowledge of its pathway in mammals is limited. In the present study, the binding of AGO and its key compounds, methyl eugenol, 1,8-cineole, and 4-allylphenyl acetate, to gamma-aminobutyric acid type A (GABAA) receptors in rat cortical membranes, was investigated using a [3H]muscimol binding assay and an in silico modeling platform. The results showed that only AGO and methyl eugenol displayed a positive modulation at the highest concentrations, whereas 1,8-cineole and 4-allylphenyl acetate were inactive. The result of AGO correlated well to the amount of methyl eugenol in AGO. Computational docking and dynamics simulations into the GABAA receptor complex model (PDB: 6X3T) showed the stable structure of the GABAA receptor-methyl eugenol complex with the lowest binding energy of -22.16 kcal/mol. This result shows that the anesthetic activity of AGO and methyl eugenol in mammals is associated with GABAA receptor modulation. An oil-in-water nanoemulsion containing 20% w/w AGO (NE-AGO) was formulated. NE-AGO showed a significant increase in specific [3H]muscimol binding, to 179% of the control, with an EC50 of 391 µg/mL. Intracellular studies show that normal human cells are highly tolerant to AGO and the nanoemulsion, indicating that NE-AGO may be useful for human anesthesia.

Masculinizing Effects of Chrysin-Loaded Poloxamer Micelles on Siamese Fighting Fish.

Siamese fighting fish (Betta splendens) are freshwater fish that are commonly found in Thailand and other Southeast Asian countries. In the present study, chrysin-loaded polymeric micelles (CPs) were developed and investigated for the masculinizing effects, survival rate, growth indices, and toxicity on Siamese fighting fish. CPs were prepared using a poloxamer. The micelle system of CPs that were formed at a chrysin-to-polymer ratio of 1:2 was found to be the most suitable monodispersed system and exhibited a nanosized diameter (74.2 ± 1.6 nm) with a narrow size distribution (0.288 ± 0.012). In vivo studies were performed using Siamese fighting fish larvae as animal models. In the in vivo toxicity study, the fish larvae were immersed in aqueous systems containing CPs that had five different chrysin concentrations of 1, 10, 100, 1000, and 10,000 ng/mL for 24, 48, and 72 h. Blank polymeric micelles and water were used as controls. The in vivo masculinization effect of CPs with different chrysin concentrations on the fish larvae was evaluated after 5 weeks of exposure. The results demonstrated that CPs with a chrysin concentration of 1000 ng/mL showed a masculinization effect of 94.59 ± 2.76% with a high fish larvae survival rate of 72.45 ± 5.09% and low toxicity. It was concluded that the developed CPs had a significant effect on the sex reversal of Siamese fighting fish larvae with a high survival rate.

Effects of Drug Concentration, Rate of Infusion, and Flush Volume on G-CSF Drug Loss When Administered Intravenously.

Purpose: This study evaluated factors that affect granulocyte-colony stimulating factor (G-CSF) adsorption in the infusion tube by measuring the G-CSF concentration, rate of G-CSF infusion, and volume of flush solution. Methods: The concentrations of G-CSF in all samples were measured by an enzyme-linked immunosorbent assay (ELISA) using human G-CSF Quantikine® ELISA kits. The concentration of G-CSF, the rate of administration, and the volume of flush solution were studied respectively. The concentration of G-CSF and the rate of administration that had a significantly lower G-CSF percent recovery after the infusion via the infusion set were used for further investigation in the study. All samples were diluted with 5% dextrose in water (D5W) to the final concentration within the standard concentration range. All experiments were performed in triplicate. Results: The concentration of G-CSF that was administered through the infusion tube at 20 µg/mL was a significantly higher G-CSF percent recovery compared with the G-CSF concentrations of 5, 10, and 15 µg/mL. The infusion rate of 15 and 20 mL/h percent recovery of G-CSF adsorption was significantly higher than the infusion rates of 30 and 40 mL/h. The concentration of G-CSF at 15 µg/mL and an infusion rate of 30 mL/h were selected to investigate the flush volumes of D5W on G-CSF adsorption. The D5W flush volume of 40 mL dramatically decreased the G-CSF adsorption with a recovery of 103 ± 1.73%. Conclusion: The G-CSF concentration of 20 µg/mL with an infusion rate of 20 mL/h, using a 40 mL D5W flush, was appropriate for intravenous G-CSF administration.

Thermosensitive Poloxamer 407/Poly(Acrylic Acid) Hydrogels with Potential Application as Injectable Drug Delivery System.

Thermosensitive hydrogels are of great interest for in situ gelling drug delivery. The thermosensitive vehicle with a gelation temperature in a range of 30-36°C would be convenient to be injected as liquid and transform into gel after injection. To prepare novel hydrogels gelling near body temperature, the gelation temperature of poloxamer 407 (PX) were tailored by mixing PX with poly(acrylic acid) (PAA). The gelation behaviors of PX/PAA systems as well as the interaction mechanism were investigated by tube inversion, viscoelastic, shear viscosity, DSC, SEM, and FTIR studies. The gelation temperature of the plain PX solutions at high concentration of 18, 20, and 22% (w/w) gelled at temperature below 28°C, which is out of the suitable temperature range. Mixing PX with PAA to obtain 18 and 20% (w/w) PX with 1% (w/w) PAA increased the gelation temperature to the desired temperature range of 30-36°C. The intermolecular entanglements and hydrogen bonds between PX and PAA may be responsible for the modulation of the gelation features of PX. The mixtures behaved low viscosity liquid at room temperature with shear thinning behavior enabling their injectability and rapidly gelled at body temperature. The gel strength increased, while the pore size decreased with increasing PX concentration. Metronidazole, an antibiotic used for periodontitis, was incorporated into the matrices, and the drug did not hinder their gelling ability. The gels showed the sustained drug release characteristic. The thermosensitive PX/PAA hydrogel could be a promising injectable in situ gelling system for periodontal drug delivery.

Glabridin.

In the title compound, C20H20O4 {systematic name: 4-[(3R)-8,8-dimethyl-3,4-dihydro-2H-pyrano[2,3-f]chromen-3-yl]benz-ene-1,3-diol}, the hydro-pyran ring linked to the pendant benzene ring adopts an envelope conformation, with the methyne C atom forming the flap. In the crystal, the -OH group at the 3-position of the benzene ring forms an O-H⋯O hydrogen bond to a chromene O-atom acceptor, whereas the -OH group at the 1-position forms an O-H⋯π inter-action with a neighboring benzene ring. The O-H⋯O hydrogen bonds form [001] chains and the O-H⋯π bonds cross-link the chains into (101) sheets. The absolute structure was assumed to be the same as that deduced from previous studies for the natural product.

Characterization of muco- and bioadhesive properties of chitosan, PVP, and chitosan/PVP blends and release of amoxicillin from alginate beads coated with chitosan/PVP.

PURPOSE: To investigate the muco/bioadhesive properties of chitosan, polyvinylpyrrolidone (PVP), and chitosan/PVP blends and the release of amoxicillin (AMX) contained in AMX-alginate beads coated with these materials. METHOD: Chitosan, PVP, and chitosan/PVP blends at various volume ratios were coated onto calcium alginate beads containing AMX. The muco/bioadhesive properties of all materials and the AMX-alginate beads coated with these materials were characterized. RESULTS: Measurements of their viscosity, texture, and adhesion to HT29 cells demonstrated that chitosan/PVP at a volume ratio of 5/5 had the best muco/bioadhesive properties when compared with chitosan, PVP, and blends of other ratios. Wash-off tests indicated that the mucoadhesive property of the coated AMX-alginate beads was significantly higher than that of the uncoated beads. Diffuse reflectance infrared Fourier transform spectroscopy showed that there were interactions between chitosan-PVP, chitosan-mucin, PVP-mucin, and chitosan/PVP blend-mucin. Scanning electron microscopy revealed that the surfaces of the coated beads were smoother than those of the uncoated beads. All coated AMX-alginate beads were able to provide a controlled release of AMX with Super Case II transport properties, at a pH of 4. This was probably a result of the rapid and extensive swelling of the alginate beads. The more rapid release of AMX at pH 1 was probably because of the rapid dissolution of the drug at this pH. CONCLUSIONS: From the controlled drug release and muco/bioadhesive properties of these coated AMX-alginate beads, we suggest that the alginate-coated beads might be a promising drug delivery system to assist with the eradication of Helicobacter pylori infections.

Characterization of cimetidine-piroxicam coprecipitate interaction using experimental studies and molecular dynamic simulations.

The crystalline states of cimetidine and piroxicam, when coprecipitated from solvents containing 1:1 mole ratio, were transformed to amorphous states as observed using powder X-ray diffraction (PXRD). Amorphous forms of drugs generally exhibit higher water solubility than crystalline forms. It is therefore interesting to investigate the interactions that cause the transformation of both the crystalline drugs. Intermolecular interactions between the drugs were determined using Fourier-transform infrared spectroscopy (FTIR) and solid-state (13)C CP/MAS NMR. Molecular dynamic (MD) simulation was performed for the first time for this type of study to indicate the specific groups involved in the interactions based on radial distribution function (RDF) analyses. RDF is a useful tool to describe the average density of atoms at a distance from a specified atom. FTIR spectra revealed a shift of the C identical withN stretching band of cimetidine. The (13)C CP/MAS NMR spectra indicated downfield shifts of C(11), C(15) and C(7) of piroxicam. RDF analyses indicated that intermolecular interactions occurred between the amide oxygen atom as well as the pyridyl nitrogen of piroxicam and H-N(3) of cimetidine. The hydrogen atom (O-H) at C(7) interacts with the N(1) of cimetidine. Since the MD simulation results are consistent with, and complementary to the experimental analyses, such simulations could provide a novel strategy for investigating specific interacting groups of drugs in coprecipitates, or in amorphous mixtures.

Crystal structure transformations and dissolution studies of cimetidine-piroxicam coprecipitates and physical mixtures.

We have recently demonstrated that coprecipitation of cimetidine (C) and piroxicam (P) at a mole ratio of 1:1 results in the transformation of the crystalline forms of both drugs to an amorphous state. In this study, coprecipitates and physical mixtures of cimetidine and piroxicam were further investigated at C/P mole ratios of 1:10, 1:5, 1:4, 1:2, 10:1, 20:1, 30:1, 40:1, and 52.5:1, the latter being the composition of a clinically used dosage. The physicochemical properties of these samples were examined using X-ray diffraction and Fourier transform infrared spectroscopy. Additionally, dissolution of piroxicam in the samples at C/P mole ratios of 10:1, 20:1, 30:1, 40:1, and 52.5:1 was investigated at pH 1.2 and pH 4. In coprecipitates with C/P mole ratios of 10:1, 20:1, 30:1, and 40:1, crystalline forms of both drugs were transformed to amorphous states. A mixture of an amorphous state and cimetidine crystalline form A was observed for the coprecipitate with a C/P mole ratio of 52.5:1. For the coprecipitates with C/P mole ratios of 1:2, 1:4, 1:5, and 1:10, cimetidine form A was transformed to form C, whereas piroxicam form II was modified to form I. It is interesting that small molecules, instead of polymers or solvents, can cause such crystal structure transformations. The dissolution of piroxicam at pH 4 is lower than that at pH 1.2. Additionally, the coprecipitates and physical mixtures with C/P mole ratios of 10:1, 20:1, 30:1, 40:1, and 52.5:1 demonstrate substantially higher dissolution of piroxicam compared to that of drug alone.