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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.

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.

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.

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.

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.

This work studied the interaction of human hemoglobin (HHb) with aminophylline, acefylline, caffeine, theophylline and diprophylline systematically by UV–vis absorption spectroscopy and fluorescence spectroscopy in combination with molecular modeling. Five alkaloids caused the fluorescence quenching of HHb by the formation of alkaloids-HHb complex. The binding constants and thermodynamic parameters were obtained. The hydrophobic and electrostatic interactions were the predominant intermolecular forces to stabilize these complexes. Results of thermodynamic analysis and molecular modeling showed that aminophylline was the strongest quencher and diprophylline was the weakest quencher.

The interactions between pepsin and four alkaloids, including caffeine (Caf), aminophylline (Ami), acefylline (Ace), diprophylline (Dip), were investigated by fluorescence, UV–visible absorption, resonance light scattering, synchronous fluorescence spectroscopy and 3D spectroscopy under mimic physiological conditions. The results revealed that Caf (Ami/Ace/Dip) caused the fluorescence quenching of pepsin by the formation of Caf (Ami/Ace/Dip)-pepsin complex. The binding constants and thermodynamic parameters at three different temperatures, the binding locality and the binding power were obtained. The hydrophobic and electrostatic interactions were the predominant intermolecular forces to stabilize the complex. Results showed that aminophylline was the stronger quencher and bound to pepsin with higher affinity than other three alkaloids.

Spectrophotometric and high-performance liquid chromatographic (HPLC) methods are developed for simultaneous determination of three binary mixtures with overlapping spectra. The spectrophotometric method is based on the use of second derivative of the ratio spectra (2DD) for resolution of three binary mixtures of indapamide with captopril (mixture 1), cinnarizine with heptaminol acefylline (mixture 2) and amoxycillin trihydrate with flucloxacillin sodium (mixture 3). The HPLC method depends on the separation of components of binary mixtures using ODS column with mobile phase consisting of acetonitrile and 5 mM aqueous heptane sulphonic acid sodium salt in ratios of (60:40, v/v, pH 5.5) for mixture 1, (50:50, v/v, pH 3.0) for mixture 2 and (35:65, v/v, pH 4.2) for mixture 3. The proposed methods are accurate, non-destructive and successfully applied for the determination of the three binary combinations in synthetic mixtures and commercial pharmaceutical products.