Kinetics study of hydrochlorothiazide lactose liquid state interaction using conventional isothermal arrhenius method under basic and neutral conditions

The Maillard reaction of hydrochlorothiazide (HCTZ) and lactose has been previously demonstrated in pharmaceutical formulations. In this study, the activation energy of - hydrohlorothiazide and lactose interaction in the liquid state was ascertained under basic and neutral conditions. Conventional isothermal High Performance Liquid Chromatography (HPLC) technique was employed to ascertain the kinetic parameters using Arrhenius method. Results: The activation energy obtained was 82.43 and 100.28 kJ/mol under basic and neutral conditions, respectively. Consequently, it can be inferred that Maillard reaction is significantly affected by pH, which can be used as a control factor whenever the reaction potentially occurs

Analytical Investigation of the Possible Chemical Interaction of Methyldopa with Some Reducing Carbohydrates Used as Pharmaceutical Excipients

Purpose: Assessment of drug substance and excipients compatibility is an important issue during pre-formulation studies as well as the quality control of pharmaceutical dosage forms. In this study, potential incompatibility between methyldopa and reducing excipients was evaluated using physicochemical methods. Methods: Dextrose and lactose (anhydrous & monohydrate) were selected as reducing carbohydrates. The initial incompatibility was studied with DSC and FTIR on binary mixtures with 1:1 mass ratio. Results were confirmed using HPLC studies coupled with mass spectrometry. Results: The DSC curves indicated the elimination of the melting endotherm of methyldopa in the binary mixtures. A new peak at 1719 cm-1 was observed in the FTIR spectra that can be attributed to the loss of type one amine functionality. The m/z of the proposed compound was observed in the mass spectra. Conclusion: The potential incompatibility of Methyldopa with reducing carbohydrates was established using physicochemical methods

Kinetics study of hydrochlorothiazide lactose liquid state interaction using conventional isothermal arrhenius method under basic and neutral conditions

ABSTRACT The Maillard reaction of hydrochlorothiazide (HCTZ) and lactose has been previously demonstrated in pharmaceutical formulations. In this study, the activation energy of - hydrohlorothiazide and lactose interaction in the liquid state was ascertained under basic and neutral conditions. Conventional isothermal High Performance Liquid Chromatography (HPLC) technique was employed to ascertain the kinetic parameters using Arrhenius method. Results: The activation energy obtained was 82.43 and 100.28 kJ/mol under basic and neutral conditions, respectively. Consequently, it can be inferred that Maillard reaction is significantly affected by pH, which can be used as a control factor whenever the reaction potentially occurs

Production and characterization of spray-dried theophylline powders prepared from fresh milk for potential use in paediatrics

"This is the accepted version of the following article: Production and characterization of spray-dried theophylline powders prepared from fresh milk for potential use in paediatrics (2017). J Pharm Pharmacol, 69: 554–566, which has been published in final form at http://dx.doi.org/10.1111/jphp.12612 . This article may be used for non-commercial purposes in accordance with the Wiley Self-Archiving Policy [http://olabout.wiley.com/WileyCDA/Section/id-820227.html]."Objective: This work evaluates the potential of using fresh milk to deliver theophylline to children.Methods: Theophylline–fresh milk systems were prepared using different solids ratios (0 : 1–1 : 0) and three fat contents in commercial milks (low, medium and high), which were spray-dried at different inlet air temperatures (Tinlet – 105, 130 and 150 °C). The process was evaluated for yield and the resulting powders for moisture content (MC), particle size and shape, density and wettability. Theophylline–milk potential interactions (differential scanning calorimetry (DSC) and FT-IR) and chemical (theophylline content) and microbiological stability of powders (shelf and in-use) were also evaluated.Key Findings: The production yield (13.6–76.0%), MC (0.0–10.3%) and contact angles in water (77.29–93.51°) were significantly (P < 0.05) affected by Tinlet, but no differences were found concerning the mean particle size (3.0–4.3 μm) of the different powders. The milk fat content significantly (P < 0.05) impacted on the density (1.244–1.552 g/cm3). Theophylline content remained stable after 6 months of storage, before extemporaneous reconstitution. After reconstitution in water, low-fat milk samples (stored at 4 °C) met the microbial pharmacopoeia criteria for up to 7 days. No theophylline–milk components interaction was observed.Conclusion: Spray-dried milk-composed powders may be used as vehicles for theophylline delivery in paediatrics following further characterization and in-vivo evaluation.info:eu-repo/semantics/publishedVersio

Preparation and In Vitro/Ex Vivo Evaluation of Buccoadhesive Discs of an Anti-Parkinson Drug: Relationship between Mucoadhesivity, Drug Release and Permeability

Background: Selegiline hydrochloride (Sel) is a drug applied for the therapy of early-step Parkinson's disease. In usual clinical doses, it is an elective irreversible MAO-B inhibitor. This study intended to formulate mucoadhesive microspheres of selegiline with the objective of improving the therapeutic efficacy, patient compliance and bioavailability. Methods: The microspheres were prepared by emulsion solvent evaporation method (O1/ O2) using hydroxypropyl methylcellulose (HPMC). In the current study, bucco-adhesive microspheres were prepared with different drug to polymer ratios and characterized by encapsulation efficiency, particle size, Differential Scanning Calorimetry (DSC), FTIR Fourier Transform Infrared Spectroscopy (FTIR), flowability, the degree of swelling and surface pH, mucoadhesive character, retentive time, and drug release studies. Results: The best drug to polymer ratio in microspheres was 1:2 (as F1). The production yield microspheres F1 showed production yield of 84.79%, mean particle size of 744.73 μm and loading efficiency of 53.33%. The DSC exhibited the property of selegiline loaded microspheres changed to amorphous form. The FTIR spectrum proposed that the drug kept its chemical stability during the emulsification process. The results showed that the microspheres of F1 had faster release than the microspheres of F2 (1:4), F3 (1:6), and commercial tablet (p<0.05). The microspheres did not exhibit good retention time properties (276.66 329.66 min). The results of mucoadhesion strength (8.3 18.3 g/cm2) and surface pH of discs (6.44 6.97) showed the better characterization of microspheres in buccal. Conclusion: The formulations were found to be appropriate candidates for the improvement of microspheres for the remedial objects

Effects of Formulation Variables and Storage Conditions on Light Protected Vitamin B12 Mixed Parenteral Formulations

Purpose: In this research the effect of vitamin B1 and B6 on cyanocobalamin stability in commercial light protected parenteral formulations and upon adding stabilizing agents will be investigated and best formulation composition and proper storage condition will be introduced. Methods: In this research some additives such as co solvents and tonicity adjusters, surfactants, antioxidants and chelating agents as well as buffer solutions, were used to improve the stability of the parenteral mixed formulations of B12 in the presence of other B vitamins (B1 and B6). Screening tests and accelerated stability tests were performed according to ICH guidelines Q1A (R2). Results: Shelf life evaluation revealed the best formulation and the proper storage condition. The results indicated the first kinetic models for all tested formulations and the optimum pH value was determined to be 5.8. There was no evidence of B12 loss when mixed with B1 and B6 in a medical syringe at room temperature for maximum of 8 hours. Conclusion: It is necessary to formulate vitamin B12 mixed parenteral solutions using proper phosphate buffers (pH=5.8) and to indicate “Store in refrigerator” on the mixed parenteral formulations of vitamin B12 with other B vitamins, which has not been expressed on the label of tested Brand formulations at the time of this study