Acefylline Research Articles

Measurement of Acefylline Piperazine Interaction and Dissociation Constants in Polymer Solvent Systems

In this study the physicochemical interactions of acefylline piperazine drug (APD) were examined in aqueous and aqueous polymer systems viz., aqueous polyethylene glycol (1.0 %w/v) and aqueous polyvinyl pyrrolidone (1.0% w/v). The study was carried within the concentration ranges from 2.0×10-2 to 10.0 ×10-2 mol/dm3 at different temperatures (293.15 to 318.15 K with the difference of 5 K). Various analytical methods such as conductometric, refractometry, and liquid chromatographic (RP-HPLC) were applied. In order to observe the interaction of APD, o m was calculated to evaluate the structural influence of polymers on the mobility of solute (APD) at different temperatures. α, Kd and Walden product of APD were also assessed in aqueous polyethylene glycol and aqueous polyvinyl pyrrolidone. Solvation was observed by Walden's product showing strong solvation of APD in water-soluble polymer systems. Thermodynamic parameters for APD such as * E , ΔG*, ΔH*and ΔS* have also been evaluated as a function of temperature to determine the exo/endothermic nature of the drug dissociation process. Specific refraction, molar refraction and polarizability of APD in aqueous and aqueous polymer systems were calculated using the Lorentz-Lorentz equation and various interactions were interpreted. Drug's compatibility studies were also performed by HPLC in aqueous and aqueous polymer systems.

Validated Smart Different Chromatographic Methods for Selective Quantification of Acefylline Piperazine, Phenobarbital Sodium and Methylparaben Additive in Bulk and Pharmaceutical Dosage Form.

Two chromatographic methods have been proposed for the simultaneous determination of acefylline piperazine (ACEF) and phenobarbital (PHENO) in presence of methylparaben as additive in pharmaceutical dosage form. The first method was thin-layer chromatography. The separation was achieved using silica gel as stationary phase and chloroform: methanol: glacial acetic acid (2.0, 8.0 and 0.1, by volume) as a developing system at 254nm. Accurate determination of both drugs was attained over the concentration range of 0.5-25μg/band. The second method was based on the use of reversed phase liquid chromatography with diode array detection, by which the proposed components were separated on a reversed phase C18 analytical column using methanol: water (60: 40, by volume) as a mobile phase with flow rate of 0.8mL/min at 214nm in a concentration range of 0.5-100μg/mL. The proposed chromatographic methods were practiced successfully for the determination of ACEF and PHENO in pharmaceutical dosage form. Both methods were validated according to the International Conference on Harmonization guidelines and statistically compared with a reported high-performance liquid chromatograph method. Planar chromatography has never been proposed in the literature for ACEF and PHENO determination besides the proposed columnar chromatographic method using an isocratic eco-friendly mobile phase.

Viscometric and FTIR studies of chloroquine phosphate, acefylline piperazine and gentamicin sulfate in aqueous-polyethylene glycol and aqueous-polyvinyl pyrrolidone at different temperatures

This paper aimed to study the effect of aqueous, aqueous polyethylene glycol (1.0 %w/v) and aqueous polyvinyl pyrrolidone (1.0 %w/v) on the physicochemical behaviour of three pharmaceuticals substantial drugs by viscosity method. Viscosity measurements of the drugs (chloroquine phosphate, acefylline piperazine and gentamicin sulfate) solutions were performed within concentration ranges from 2.0 × 10 −2 to 10.0 × 10 −2 ± 0.001 mol.dm −3 at varying temperatures (293.15, 298.15, 303.15, 308.15, 313.15 and 318.15 ± 0.01 K). The viscosity data used to interpret the interactions (drug-drug and drug-solvent) existing in the solutions of drugs in terms of ‘ A ’ and ‘ B ’ coefficients of Jones–Dole equation respectively. Temperature derivatives of the B -coefficient ( dB / dT ) were also calculated which help to establish the relation between the nature of the solute and the structural modifications in the solution. Hence, the structure promoting ability of the AP in aqueous system and structure destroying effect of CP, AP and GS in the aqueous-polymeric system was observed. The FTIR studies of CP, AP and GS show that the chemical identity of the drug was not affected by the polymers and no binding of the new forming compound was detected.

Validated RP-LC Methods for Investigating the Degradation Behavior of Acefylline: Application for Analysis in Two Binary Mixtures

Background: Acefylline (Acef) is a derivative of theophylline that has bronchodilator effects. Two binary mixtures were marketed for Acef: Acefylline piperazine/ Phenobarbitone (Acef-P/Phen) and Acefylline heptaminol/ Cinnarizine (Acef-H/ Cinn). To our knowledge none of the reported methods had the capacity to determine Acef in its binary mixture in presence of its degradation products and potential impurity theophylline (Theo). Methods: Two validated RP-LC methods were established for the determination of Acef-P/Phen and Acef-H/ Cinn in presence of Acef degradation products and its potential impurity Theo. A complete study of the forced acidic, alkaline and oxidative degradation of Acef was presented. The methods were based on LC separation on RP C18 columns using isocratic and gradient elution for Acef-P /Phen and Acef-H /Cinn mixtures, respectively. Different chromatographic conditions were examined and optimized. Results: Linear responses were attained over concentration ranges of 75-500/15-1000 μg/mL and 100-1000 /50- 500 μg/mL with mean percentage recoveries of (100.72±1.23)%/ (99.29±1.12)% and (100.44±1.27)%/ (99.01±0.97)% for Acef-P/Phen and Acef-H /Cinn, respectively. ICH guidelines were used for methods validation and all parameters were found to be acceptable. Conclusion: The methods showed to be accurate, precise and specific for the analysis of Acef-P/Phen and AcefH /Cinn in drug substance, drug product and in laboratory prepared mixtures in presence of Theo and up to 50% of degradation products. The structures of the main degradation products and the expected degradation pathway were suggested using the MS data.

Commentary on «Structure breaking/making property of acefylline piperazine in aqueous, aqueous methanol, and aqueous ethylene glycol systems»

A polemic is given concerning the volumetric properties for acefylline piperazine dissolved in water reported in the published paper by Masood and coworkers. The authors' measured densities and apparent molar volumes are not consistent with values given in a published follow-up study.

Drug-drug and drug-solvent interaction studies of Chloroquine phosphate, Acefylline piperazine and Gentamicin sulfate in polymeric systems

The densities of three pharmacologically significantly used drugs i.e., Chloroquine phosphate (CP), Acefylline piperazine (AP) and Gentamicin sulfate (GS) have been carried out in aqueous (aq), aqueous polyethylene glycol (aq-PEG) and aqueous polyvinyl pyrrolidone (aq-PVP) solvent systems within concentration range (0.02–0.1 ± 0.001 mol.dm−3) at different temperatures (293.15–318.15 K) with the interval of 5 K. Density data were used to evaluate volumetric properties of drugs (CP, AP and GS) by apparent molar volume, partial molar volumes, molar expansibilities and isothermal expansion coefficient. ϕE° provides information about the absence or presence of a caging or packing effect. Partial molar transfer volume was also calculated to study the hydrophilic/hydrophobic interactions in aq-PEG and aq-PVP solvent systems. The results are interpreted in terms of drug–solvent and drug-drug interactions and structure making or breaking abilities of drugs in aq, aq-PEG and aq-PVP solvent systems.

Validated Eco-Friendly Spectrophotometric Methods for the Determination of Acefylline Piperazine and Bromhexine Hydrochloride in the Presence of Dosage Form Additives

Four simple, precise, accurate, and eco-friendly spectrophotometric methods manipulating ratio spectra were used for the determination of acefylline piperazine (AC) and bromhexine hydrochloride (BR) in the presence of two dosage form additives — methylparaben (MP) and propylparaben (PP). The dual wavelength in ratio spectra (DWRS) and derivative of double divisor of ratio spectra (DD-RS) methods were used for the simultaneous determination of AC and BR. The first derivative ratio zero crossing method (1DD) was used for the determination of BR. AC can be determined using sequential spectrophotometry, where the ratio subtraction method was applied to remove the extended spectrum of BR followed by applying the dual wave length method. The linearity of the proposed methods was investigated in the ranges 5.00–60.00 and 4.00–60.00 μg/mL for AC and BR, respectively. The selectivity of the developed methods was investigated by analyzing laboratory-prepared mixtures containing different ratios of the cited drugs and additives in addition to the analysis of their pharmaceutical dosage form. The validity of the proposed methods was further assessed using the standard addition technique. The obtained results were statistically compared with those obtained by the reported method, showing no significant difference with respect to their accuracy and precision at p = 0.05.

Optical studies of acefylline piperazine, chlorpheniramine maleate, thiamine hydrochloride in aqueous, aqueous methanol and aqueous ethylene glycol systems

Refractive index, FTIR and Uv–vis absorption study of acefylline piperazine, chlorpheniramine maleate, thiamine hydrochloride was done to investigate the solute-solvent interactions. The interaction of drugs (AP, CPM, TAD) studied in aqueous, aqueous methanol and aqueous ethylene glycol systems at 303 K. Specific refraction, Molar refraction and polarizability of drugs in aqueous and aqueous alcoholic systems was calculated by using Lorentz-Lorentz equation. FTIR study of drugs in aqueous and aqueous alcoholic systems was undertaken to analyze the compatibility of drugs in studied systems. The UV–vis absorption study has also been done to interpret the interaction patterns occurring in drugs and solvent systems.

Green monitoring of bromhexine oxidative degradation kinetics

Kinetics studies are important in quality control to assure the safety and efficacy of the pharmaceutical compounds. Recently, potentiometric ion-selective electrodes (ISEs) breakthrough kinetics study due to their ability to provide real-time measurements which meet “green analytical chemistry” (GAC) principles. A polyvinyl chloride (PVC) matrix membrane was fabricated to monitor bromhexine (BR) oxidative degradation kinetics using tetraphenylborate as a cation exchanger. At-line monitoring of the oxidative degradation kinetics of BR was performed; by continuous measuring the decrease in the sensor potential over time. So a real-time observation and a continuous profile were obtained for the oxidation of BR under various H2O2 concentrations and temperature. This kinetic study determines the oxidation activation energy that was 6.4 kcal mol−1. To expand the application of this sensor, BR was determined in bulk powder and dosage form in the presence of both co-formulated drug (acefylline piperazine) and dosage form additives. The proposed sensor had been characterized according to IUPAC recommendations and a linear dynamic range was 5 × 10−6 to 1 × 10−3 M and other sensor parameters had been calculated.

Structure Breaking/Making Property of Acefylline Piperazine in Aqueous, Aqueous Methanol, and Aqueous Ethylene Glycol Systems

Densities of acefylline piperazine (AP) in aqueous, aqueous methanol, and aqueous ethylene glycol (10% v/v) systems are determined in the concentration range 0.04-0.14±0.001 mol/dm3 at different temperatures (298.15-318.15 K) with the interval of 5 K. The apparent molar volume (φv), the partial molar volume $$(\phi_v^0)$$ , and the ion-ion interaction parameter (Sv) are calculated using the Masson equation. Partial molar expansibilities $$(\phi_E^0)$$ , which indicate the presence or absence of the caging or packing effect, are also evaluated and discussed. The results are interpreted in terms of solute-solvent and solute-solute interactions of AP in aqueous, aqueous methanol, and aqueous ethylene glycol systems. The structure-breaking and structure-making properties of AP are inferred by the sign of Hepler′s criterion $$(\partial^2\phi_v^0/\partial{T}^2)_p$$ , i.e. the second derivative of the partial molar volume with respect to the temperature at the constant pressure.

Structure breaking/making property of acefylline piperazine in aqueous, aqueous methanol and aqueous ethylene glycol systems

Structure breaking/making property of acefylline piperazine in aqueous, aqueous methanol and aqueous ethylene glycol systems