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The development and validation of two uncomplicated, selective, and non-extraction-based visible spectrophotometric methods was carried out for the quantification of a tricyclic antidepressant amitriptyline hydrochloride as pharmaceutical tablets as well as in its pure form. The methods rely on the formation of ion pair complexes between amitriptyline base and two acidic dyes, bromothymol blue and bromocresol purple, which were subsequently measured at 410 and 400 nm, respectively. The developed methods included numerous reaction variables that were examined and improved. Beer's law is applicable under optimal conditions for the bromothymol blue and bromocresol purple methods, respectively, over concentrations from 0.5 to 12.5 μg mL−1 and from 0.5 to 10.0 μg mL−1 amitriptyline hydrochloride. The computed values of molar absorptivity were 1.79 × 104 and 2.32 × 104 L.mol−1.cm−1 for bromothymol blue and bromocresol purple methods, respectively, with Sandell's sensitivity values of 0.0155 and 0.0119 μg cm−2. Both detection limits and quantification limits were computed and determined to be 0.55 and 1.67 μg mL−1 for bromothymol blue method, and 0.49 and 1.49 μg mL−1 for bromocresol purple method, respectively. The developed methods were successfully applied to estimate the concentration of amitriptyline hydrochloride in bulk form and commercial pills. Therefore, these methods demonstrate promising potential for testing this drug in labs for quality control. Spectrophotometric quantification of amitriptyline hydrochloride in pharmaceutical tablets: method development and validation [ABSTRACT FROM AUTHOR]

The purpose of the current work is to explore the interactions between antidepressant drug amitriptyline hydrochloride (AMT, an amphiphilic) and Triton-165 (TX-165, a nonionic surfactant) by applying surface tension, and UV–visible spectroscopy methods. In diverse solvents (aqueous system/50 mmol kg−1 NaCl/500 mmol kg−1 urea), experimental results using the surface tension technique revealed non-ideal behavior along with attractive/synergistic interactions at interface among the AMT drug and TX-165 mixed systems. As contrasted with aqueous system, NaCl media boosted the interfacial properties, resulting in increased synergism/attractive interaction between ingredients (AMT and TX-165), while urea media had the opposite effect. Numerous interfacial parameters such as surface excess concentration (Γmax), surfactant composition at mixed monolayer ( X 1 σ ), interaction parameters (βσ) activity coefficient [f1σ (TX-165) and f2σ (AMT)], and minimum area per molecule ( A min ) were assessed and illustrated in detail. Interaction parameters (βσ) at surface were attained negative in each case revealing the attractive/synergism among the constituents. It was found that the Gibbs energy of adsorption ( Δ G ads ∘) throughout all utilized solvent was negative, which indicates spontaneity in the adsorption phenomena. AMT + TX-165 mixtures show synergistic or attractive interactions and non-ideal mixing behaviors at surface depending on mixture composition. In addition, UV–visible analysis detected peak shifts and a surge in absorbance during the interaction of TX-165 with TX-165. It was suggested in the current study that TX-165 surfactant could be used for effective drug delivery of antidepressants. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the physicochemical and microbiological stability of extemporaneous amitriptyline hydrochloride (AMH) topical preparations for the treatment of neuropathic pain. Materials and Methods: AMH tablets were triturated to produce fine powders with a mortar and pestle. These powders were levigated and separately incorporated into four compounding bases: hydrophilic petrolatum USP, anionic cream, cold cream USP, and pluronic lecithin organogel (PLO) having the concentration of 2%w/w AMH. Results: In the in vitro release study, the most significant amount of AMH was released from the PLO, followed by cold cream, anionic cream and hydrophilic petrolatum, respectively; therefore, the compounded AMH in cold cream and AMH in PLO were selected for the evaluation of the in vitro permeation and product stability. The permeation of AMH from PLO across human epidermal membrane was significantly greater than that from the cold cream. Product stability was characterized as having no remarkable change in color or texture and AMH remaining in the range of 90-110% of the initial concentration quantified by high-performance liquid chromatography. Compounded AMH in cold cream was stable at 2-8 °C and 30 °C for 60 days, and 40 °C for 30 days, whereas compounded AMH in PLO was stable at 30 °C and 40 °C for 14 days. There was no visible microbial growth in any of the samples. Conclusion: Taken together with the in vitro permeation and product stability studies, the present study suggests that AMH in cold cream could be prepared and used as extemporaneous topical preparations with a beyond-use date of 60 days when kept at 2-8 °C and 30 °C. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the physicochemical and microbiological stability of extemporaneous amitriptyline hydrochloride (AMH) topical preparations for the treatment of neuropathic pain. Materials and Methods: AMH tablets were triturated to produce fine powders with a mortar and pestle. These powders were levigated and separately incorporated into four compounding bases: hydrophilic petrolatum USP, anionic cream, cold cream USP, and pluronic lecithin organogel (PLO) having the concentration of 2%w/w AMH. Results: In the in vitro release study, the most significant amount of AMH was released from the PLO, followed by cold cream, anionic cream and hydrophilic petrolatum, respectively; therefore, the compounded AMH in cold cream and AMH in PLO were selected for the evaluation of the in vitro permeation and product stability. The permeation of AMH from PLO across human epidermal membrane was significantly greater than that from the cold cream. Product stability was characterized as having no remarkable change in color or texture and AMH remaining in the range of 90–110% of the initial concentration quantified by high-performance liquid chromatography. Compounded AMH in cold cream was stable at 2–8 °C and 30 °C for 60 days, and 40 °C for 30 days, whereas compounded AMH in PLO was stable at 30 °C and 40 °C for 14 days. There was no visible microbial growth in any of the samples. Conclusion: Taken together with the in vitro permeation and product stability studies, the present study suggests that AMH in cold cream could be prepared and used as extemporaneous topical preparations with a beyond-use date of 60 days when kept at 2–8 °C and 30 °C.

You Zhai,1,2 Lihua Wu,1,2 Yunliang Zheng,1,2 Minglan Wu,1,2 Yujie Huang,1,2 Qian Huang,1,2 Jianzhong Shentu,1– 3 Qingwei Zhao,1,2 Jian Liu1,2 1Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3College of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaCorrespondence: Jian LiuResearch Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, People’s Republic of ChinaTel +86 571 87236537Fax +86 571 87214223Email lindaliu87@zju.edu.cnPurpose: This study compares the pharmacokinetic and safety profiles between a new generic and a branded reference formulation of amitriptyline hydrochloride tablets, and assesses the bioequivalence of the two products in healthy Chinese volunteers to obtain sufficient evidence for the marketing approval of the generic drug.Materials and Methods: A randomized, open-label, two-period crossover study (clinicaltrials.gov, NCT03646526) was conducted under both fasting and fed conditions in healthy Chinese volunteers (24 subjects/condition). Eligible subjects randomly received a single 25 mg dose of either the test or the reference formulation, followed by a 3-week washout period. Blood samples were collected until 144 h following administration. The pharmacokinetic parameters were acquired based on the concentration-time profiles, including the areas under the plasma concentration-time curve (AUC0-t, AUC0-∞), the peak plasma concentration (Cmax), the time to achieve Cmax (Tmax), and the elimination half-life (t1/2). The geometric mean ratios (GMRs) and the corresponding 90% confidence intervals (CIs) of amitriptyline were acquired for bioequivalence analysis, and values of these parameters for nortriptyline were used for comparison of therapeutic outcomes. Safety assessments included laboratory tests, physical examination, vital signs, and incidence of adverse events (AEs).Results: The values of t1/2 and Tmax for amitriptyline were not significantly different between the test and reference products under both fasting and fed conditions (P > 0.05). The GMRs of Cmax, AUC0–t, and AUC0-∞ between the two products, and corresponding 90% CIs, were all within the range of 80% to 125% under both fasting and fed conditions. The test and reference products were well tolerated and did not elicit serious adverse events.Conclusion: This study demonstrated that the generic and reference products were well tolerated by the subjects and bioequivalent, according to the rate and extent of the drug absorption.Keywords: bioequivalence, pharmacokinetics, amitriptyline hydrochloride, nortriptyline

Amitriptyline hydrochloride (AT) is a drug used especially for depression and migraines. In this study, new molecularly imprinted polymers (MIPs) were prepared as a drug carrier for AT to increase the half‐life of the drug and consequently reducing drug‐related problems. MIPs synthesized by precipitation polymerization method. Methacrylic acid (MAA) as a monomer and Trimethylolpropane trimethacrylate (TRIM) as a cross‐linker were used for polymerization. To obtain optimized properties for MIPs, the effect of crucial parameters including solvent variety, solvent ratios, different molar ratios of AT:MAA: TRIM, the impact of time and concentration of the drug solution on loading efficiency was studied. The prepared samples were structurally characterized by FT‐IR, FE‐SEM, TGA, DSC, DLS, and BET to confirm the optimization of MIPs. Also, in‐vitro drug release has been carried out in simulated intestinal fluid (SIF, pH = 7.4) by measuring the absorbance at λ max = 239 nm by UV–Vis spectrophotometer. The results showed that the synthesized nanosphere particles presented uniform surface morphology and high thermal resistance characteristics. Besides, MIPs have uniform distribution sites molecular with nano‐sized particles, which is ideal for drug delivery. Kinetic study on prepared samples showed that the MIPs were fitted by the Korsmeyer–Peppas model, release study presented that the MIP2 and MIP8 presented more controlled release compared to the other samples. The obtained data confirmed the designed carriers satisfactorily meet the requirements in sustained and controlled drug delivery applications. [ABSTRACT FROM AUTHOR]

A simple, precise and sensitive UV method has been developed for the estimation of Amitriptyline Hydrochloride in bulk drug form by Difference Spectroscopic method. Amitriptyline Hydrochloride has exhibited maximum absorbance at about 239nm in acidic and basic media. Beer’s law was obeyed in the concentration range of (2-10) μg/ml in both cases. The proposed method was successfully applied for the determination of Amitriptyline Hydrochloride in bulk drug. As per ICH guidelines the results of the analysis were validated statistically and were found to be satisfactory. [ABSTRACT FROM AUTHOR]

Aim: To investigate the enhancement of bioavailability by the usage of drug nanoparticles for increasing the efficacy of antidepressant therapeutic value. Materials & methods: Nano-amitriptyline HCI (AMT·HCl) particles were successfully prepared via a simple spray freeze drying (SFD) method. Results: The as-prepared nanoparticles are amorphous instead of crystalline. The mean size of AMT·HCl nanoparticles is 90 nm. In in vitro evaluation, AMT·HCl nanoparticles have greatly improved the dissolution compared with pure bulk materials, which have potential for enhancing human bioavailability and diminishing toxic effect. A nanoparticle formation mechanism was also proposed. Conclusion: These findings promote the development of antidepressant therapeutic evaluation based on the usage of AMT·HCl nanoparticles by SFD method and indicate that SFD is an alternative for a range of nanoparticle preparation in industrial pharmacy. [ABSTRACT FROM AUTHOR]

Abstract The thermodynamics and interfacial behavior of the mixed micellization of a trisubstituted imidazolium based surface active ionic liquid (SAIL), 1-dodecyl-2,3-dimethylimidazolium chloride [C 12 bmim][Cl], with an antidepressant amphiphilic drug amitriptyline hydrochloride (AMT) have been studied by employing surface tension measurements at 298.15 K and from conductance at 288.15, 298.15 and 308.15 K. Critical micelle concentration (cmc), degree of ionization (α), and other thermodynamic parameters like Gibbs free energy of micellization (∆G mic. °), standard enthalpy of micellization (∆H mic. °) and standard entropy of micellization (∆S mic. °) were derived from conductivity measurements. The respective surface active parameters like surface tension at cmc (γ cmc), minimum surface area per ionic liquid molecule (A min), adsorption efficiency (pC 20), maximum surface excess concentration (Г max), effectiveness of surface tension reduction (Π cmc), and cmc of the mixed systems of SAIL and AMT have been cognized using surface tension measurements. The negative values of ∆G mic. ° and the standard Gibbs free energy of adsorption at the air/water interface (∆G ad. °) indicate the feasibility of the micellization behavior of the mixed systems and confirm the feasibility of drug-SAIL interactions. The micellar interaction parameter (β m ) have also been analyzed to get detailed insights of the interactions between the amphiphilic drug and the SAIL by applying theoretical model introduced by Rubingh and Motomura. The negative value of this parameter indicates the presence of synergistic interactions of SAIL-AMT binary mixtures. A comparative study has been done between disubstituted and trisubstituted SAILs and it has been found that the surface activity of trisubstituted SAIL is better than their disubstituted analogue due to the high hydrophobicity and hydrophilicity of trisubstituted SAIL. Highlights • A trisubstituted imidazolium based SAIL has been synthesized. • Mixed micellization of SAIL with AMT drug has been analyzed. • The study confirms the synergistic interactions between the drug and the SAIL. [ABSTRACT FROM AUTHOR]

Herein we provide a detailed result about the effect of various additives, viz. inorganic salts, quaternary ammonium bromides (QABs) and amino acids on clouding behavior of amphiphilic drug amitriptyline hydrochloride (AMT). The continuous increase in the cloud point (CP) of drug by increase in inorganic salt concentration and the magnitude of increases rely upon the position of the salts in Hofmeister series and hydrated radii. The QABs also influence continuous increase in the CP, which is illustrated in terms of the alkyl chain length of peculiar QAB. The effect of amino acids on CP of the drug solution is dependent upon the characteristics (acidic, basic, polar or nonpolar) of particular amino acids. The overall behavior of additives has been analyzed and discussed on the basis of electrostatic repulsion or interaction, micellar growth, and mixed micelle formation between the ingredients. In addition to this, thermodynamic parameters are also evaluated.

Purpose: To investigate the effects of combined treatment of amitriptyline hydrochloride tablets and fluoxetine hydrochloride on therapeutic indicator levels in depressive patients. Methods: Patients with depression (n = 104) were divided into control group and study group (52 cases each) using random number table method. Control group was treated with oral fluoxetine hydrochloride (FH) tablets only, while the study group received amitriptyline hydrochloride tablets, in addition to fluoxetine hydrochloride tablets. Both treatments lasted 3 months. Clinical effects and thyroid function indices were determined and compared for the two groups. Results: Treatment effectiveness in the study group (92.3 %) was markedly higher than that in control group (75.0 %, p < 0.05). In both groups, Pittsburgh Sleep Quality Index, Hamilton Depression Scale and Hamilton Anxiety Table scores significantly decreased post-treatment (p < 0.05). In contrast, there was significant increase in γ-aminobutyric acid (GABA) and serotonin (5-HT) levels in the two groups. In both groups, T3 and T4 significantly decreased while thyroid stimulating hormone (TSH) increased significantly (p < 0.05). Thyroid function in the study group was markedly higher than in the control group (p < 0.05). Conclusion: Combination treatment with amitriptyline hydrochloride tablets and FH is more effective than FH alone in the treatment of patients with depression. The combined treatment has a high degree of safety and is recommended for clinical application. [ABSTRACT FROM AUTHOR]

The mixed micellization behavior of surface active ionic liquids (SAILs), 1-dodecyl-3-methylimidazolium chloride, [C 12 mim][Cl], and 1-tetradecyl-3-methylimidazolium chloride, [C 14 mim][Cl] with an amphiphilic drug amitriptyline hydrochloride (AMT) have been studied using surface tension and conductance. Interfacial parameters obtained from surface tension were beneficial in deciphering the phenomenon taking place at the interface. Critical micelle concentration ( cmc ), and various thermodynamic parameters were achieved from conductance. The negative values of Δ G mic . ∘ and Δ G ad . ∘ indicate the feasibility of the mixed micellization process. Rubingh and Motomura introduced theoretical model for micellar interaction parameter ( β m ) have been examined to investigate the interactions between AMT and the SAILs. [ABSTRACT FROM AUTHOR]

Abstract: Spectrophotometric studies were successfully used in quantitative analysis of Amitriptyline Hydrochloride (ATH) Two new methods using spectrophotometry are described for the determination of (ATH) with potassium bromate as the oxidizing agent and acid dyes, Methyl orange and Indigo carmine. Both spectrophotometric methods are based on the oxidation of mentioned drugs by a known excess of bromate in acid medium and in the presence of excess of bromide followed by estimation of surplus oxidant by reacting with either Indigo carmine (method A) or Methyl orange (method B), and measuring the absorbance at 609 or 507 nm

Abstract: The cloud point (CP) and thermodynamic parameters at cloud point viz., ΔsG0, ΔsH0and TΔsS0 of an amphiphilic drug amitriptyline hydrochloride (AMT) at several compositions of organic solvent‐water namely, ethylene glycol (EG) / glycerol (GL) ‐ water (WR) (0%, 5%, 10%, 15%, 20%, 25%, 30%, 35% and 40% w/w) mixed media and the effects of addition of conventional hexadecyltrimethylammonium bromide (CTAB), tetradecyltrimethylammonium bromide (TTAB) and gemini (14‐4‐14, 14–5‐14 and 14–6‐14) surfactants at selected compositions of organic solvent‐water media (0%, 5%, 10%, 15% and 20%, w/w) have been studied at a pH 6.7. Conductivity measurements were done to determine the critical micelle concentration (cmc) and degree of counterion dissociation (α) of AMT in water and different weight% of binary mixture ranging from 0% to 25% of EG/GL at 30 °C. It is observed that the micellization of AMT molecules is affected through an indirect, solvent‐mediated mechanism with the increase in their binary mixture due to lowering of dielectric constant of the mixed media. As a result, inter / intra electrostatic repulsion in the drug‐micellar head groups increases raising the cmc values of AMT. The study reveals that the inclusion of EG and GL to the AMT drug solution with/without additives modifies the interactions of the drug molecules due to a decrease in dielectric constant of resultant mixed media. [ABSTRACT FROM AUTHOR]

The removal of three emerging contaminants (ECs) (amitriptyline hydrochloride (AH), methyl salicylate (MS) and 2-phenoxyethanol (PE)) dissolved in several water matrices by means of their adsorption onto powdered activated carbon (PAC) and granular activated carbon (GAC) has been investigated. When dissolved in ultrapure water, adsorption of the ECs followed the trend of AH > MS > PE, with a positive effect of the adsorbent dose. According to the analysis of the adsorption isotherms and adsorption kinetics, PAC showed strongly higher adsorption efficiency in both capacity and velocity of the adsorption, in agreement with its higher mesoporosity. Equilibrium isotherm data were fitted by Langmuir and Freundlich models. Pseudo-second order kinetics modeled very successfully the adsorption process. Finally, the effect of the presence of dissolved organic matter (DOM) in the water matrices (ultrapure water, surface water and two effluents from wastewater treatment plants) on the adsorption of the selected ECs onto PAC was established, as well as its performance on the removal of water quality parameters. Results show a negative effect of the DOM content on the adsorption efficiency. Over 50% of organic matter was removed with high PAC doses, revealing that adsorption onto PAC is an effective technology to remove both micro-pollutants and DOM from water matrices. [ABSTRACT FROM PUBLISHER]

[Display omitted] • Interaction of amitriptyline hydrochloride (AMT) with TX-165 in aqueous/NaCl/urea media. • Surface tension/FT-IR/molecular dynamics simulation techniques were used. • TX-165 was found in higher fraction than AMT in the mixed micelles. • Thermodynamic studies revealed that mixed micelle formation is spontaneous. • FT-IR investigation also detected interaction amongst AMT and TX-165. Herein, mixed micellization behavior of the antidepressant drug amitriptyline hydrochloride (AMT) + nonionic surfactant triton X-165 (TX-165) mixtures were investigated thoroughly using various techniques. Dullness and depression are treated with AMT. Effect of different media of fixed concentration (aq./50 mmol kg−1 NaCl/500 mmol kg−1 urea) was exposed on the AMT interaction with TX-165 by tensiometry technique at 298.15 K. For AMT + TX-165 mixture, the assessed critical micelles concentration (cmc) was achieved lower compared with calculated ideal cmc value (cmc *) of respective system as a result of the nonideal behavior of mixed system. AMT and TX-165 interaction in aq. NaCl solvent was more pronounced than aqueous solution but was less apparent when using urea solution, i.e., AMT interacted with TX-165 in different solvents as given order: NaCl > aqueous > urea. As a result of TX-165′s higher hydrophobicity, TX-165 accomplished to have a more fraction in mixed micelles compared with AMT. The micellar composition of TX-165 (X 1 R ub ) was attained larger than the corresponding employed mole fraction of TX-165 (α 1) with exception at α 1 = 0.9. It was found that in all cases, the interaction parameter (β Rub) was negative, indicating a synergistic/attractive interaction between AMT and TX-165. Thermodynamic studies have revealed that the formation of mixed micelles of AMT + TX-165 is worthwhile, as well as spontaneous. The Gibb's free energy (Δ G m °) value of studied system was found negative in each employed solvent showing the spontaneity of system, and spontaneity was highest with NaCl and lowest with urea than in aqueous solution. FT-IR spectra revealed the shifting of wavelength of constituent mixture compared with singular employed constituent, which elucidates the interaction amongst them. The interactions between AMT and TX-165 were revealed on the atomic scale using molecular dynamics simulation, demonstrating good agreement with the results of the experiments. Considering these results, a drug delivery system might be developed. [ABSTRACT FROM AUTHOR]

• Interaction of amitriptyline hydrochloride (AMT) with ionic liquid were studied. • Clint, Motomura, Rubingh, Rosen, etc. hypothetical models were used. • Activity coefficients were found below one, exhibiting interactions amongst constituents. • FTIR/UV–visible spectroscopy was also used to estimate interactions amid components. • Current results show that ionic liquid possibly will be effective drug delivery vehicle. Mixtures of an antidepressant drug, amitriptyline hydrochloride (AMT), and ionic liquid, 1-hexadecyl-3-methylimidazolium chloride (HMICl), were investigated by tensiometry at a temperature of 298.15 K with diverse mole fraction (α 1) of HMICl to determine the association, surface, and thermodynamic properties. Fourier transform infrared (FTIR) and UV–visible spectroscopy were also used to estimate the interactions between AMT and HMICl. AMT can treat depression, anxiety, and other mental illnesses. Imidazolium-based surface-active ionic liquids are ideal for biomedical uses because of their unique physicochemical properties. The interaction between AMT and HMICl was also examined using non-aqueous solvent systems (500 mmol·kg−1 urea and 250 mmol·kg−1 glucose). The ideal cmc (cmc id) measured for the mixed system (AMT + HMICl) tensiometry was notably smaller than the critical micelle concentration (cmc). As a result, AMT and HMICl interact fairly well, and interaction also increased when the α 1 of HMICl increased. The cmc values for pure and mixed solutions in urea were higher than those in aqueous, while in glucose, they were lower. Hypothetical models, including those of Clint, Motomura, Rubingh, and Rosen, have been used to determine the association, interfacial, and thermodynamic properties. For each constituent, the activity coefficients were consistently < 1 for micellar along with interface, exhibiting the intermolecular interactions amongst constituents as well as nonideal behavior. The excess free energy was negative in each case, implying that mixed micelles and monolayers have higher stability than micelles and monolayers of single components. The direct interaction of AMT and HMICl was also characterized by FTIR and UV–visible analysis, similar to the tensiometric method. In summary, the ionic liquid HMICl may be an effective drug delivery vehicle. [ABSTRACT FROM AUTHOR]

Conductivity method was carried out at various temperatures ranging from 293.15 K to 313.15 K to examine the monomeric as well as micellar phases of aqueous/brine/urea solutions of mixed systems composed of anionic surfactant sodium dodecyl sulfate (SDS) and cationic drug amitriptyline hydrochloride (AMT). AMT is used to treat mental/mood problems such as depression. NaCl decreases critical micelles concentration ( cmc ) of pure components as well as their mixed systems may be mainly ascribed to the salting-out effect of the hydrophobic moiety of components while urea increases the cmc value because of enhancement in the surface charge of the micelles/mixed micelles. The interaction among the monomers in the micelles/mixed micelles in the urea solution is slightly less than the NaCl and aqueous solutions. Synergism is modeled by employing the regular solution theory (RST) with a negative interaction parameter and nonideal behavior. Molecular thermodynamic models of Rubingh, Rodens and Motomura allow the calculation of the total excess free energy of micellization (Δ G ex ) with negative values in all the three situations. The aggregation number, micropolarity, and apparent dielectric constant of solution mixtures were evaluated and discussed in detail by fluorescence measurement in three different media. [ABSTRACT FROM AUTHOR]

Poly (vinyl chloride) membrane electrodes for the determination of amitriptyline hydrochloride were fabricated based on the use of amitriptyline-molybdovanadate and amitriptyline-molybdotungstate as electroactive materials and dioctylphthalate as the plasticizing agent. The effect of membrane composition on the electrode response was studied. The membrane electrodes containing amitriptyline-molybdovanadate (electrode A) and amitriptyline-molybdotungstate (electrode B) showed a fast and stable response over the amitriptyline hydrochloride concentration range 1.0 × 10 − 4 –1.0 × 10 − 2 mol L − 1 . Under the optimum conditions, the slope of the calibration curve, and detection limits were found to be − 36.2 mV/decade; − 40.81 mV/decade and 6.87 × 10 − 5 ; 6.73 × 10 − 5 mol L − 1 , for electrodes A and B, respectively. The life span of both the electrodes was found to be more than 2 months. The isothermal coefficient of electrodes A and B amounted to 0.00070 V/°C and 0.00068 V/°C, respectively. Both the electrodes were successfully applied to the determination of amitriptyline hydrochloride in tablets and water samples by direct potentiometric method. [ABSTRACT FROM AUTHOR]

The thermodynamics of mixed micellization of amitriptyline hydrochloride (AMT) with ionic liquid-type imidazolium gemini surfactant ([C-4-Cim] Br), was investigated at different mole fractions and temperatures by surface tension measurements. The deviation of the critical micelle concentration (CMC) from the ideal critical micelle concentration (CMC *), micellar mole fraction ( $$X_{1}^{m}$$ ) from ideal micellar mole fraction ( $$X_{1}^{\text{ideal}}$$ ), the values of interaction parameter ( $$\beta$$ ) and activity coefficients ( $$f_{i}$$ ) (for both mixed micelles and mixed monolayer) explained the non-ideal behavior (i.e., synergistic behavior) of binary mixtures. The excess free energy (∆ G) for the AMT-[C-4-Cim] Br binary mixtures explained the mixed micelles stability in comparison to micelles of [C-4-Cim] Br and pure AMT. Interfacial parameters, i.e., Gibbs surface excess ( $$\varGamma_{\hbox{max} }$$ ), minimum head group area at air/water interface ( $$A_{\hbox{min} }$$ ), free energy of micellization ( $$\Delta G_{m}^{o}$$ ), and standard Gibbs energy of adsorption (∆ G) were also evaluated for the systems. The standard entropy of adsorption (∆ S) was found higher than the standard entropy of micellization (∆ S) at all mole fractions of AMT ( α). [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the effect of different viscosity grade hydroxy propyl methyl cellulose polymers (HPMC K4M, HPMC K15M and HPMC K100M) in different combinations in the design of amitriptyline hydrochloride transdermal film. The films were prepared (F1 to F15) by solvent evaporation method and subjected to in vitro evaluation such as physicochemical properties of thickness, folding endurance, % moisture loss, % moisture absorption, drug content, in vitro drug release, release kinetic and skin permeation. The compatibility was tested by Fourier Transform Infrared Spectroscopy (FTIR). The FTIR spectra revealed the compatibility among the drug and the polymers. The films were found to possess suitable physicochemical properties having uniform thickness and drug content. The film F14 (combination of HPMC K4M and HPMC K100M at a ratio of 3:4) showed significantly (P<0.5) highest percentage of amitriptyline HCl release. Maximum release of 97.23±2.11% and a skin permeation of 85.50±3.11% were obtained for the formulation F14 over a period of 24h. It can be concluded that the drug release could be modulated using different combinations of HPMC polymers. The HPMC K4M and HPMC K100M combination at a ratio of 3:4 was suitable in the transdermal delivery of amitriptyline HCl. [ABSTRACT FROM AUTHOR]

Herein we provide a detailed result about the effect of various additives, viz. inorganic salts, quaternary ammonium bromides (QABs) and amino acids on clouding behavior of amphiphilic drug amitriptyline hydrochloride (AMT). The continuous increase in the cloud point ( CP ) of drug by increase in inorganic salt concentration and the magnitude of increases rely upon the position of the salts in Hofmeister series and hydrated radii. The QABs also influence continuous increase in the CP , which is illustrated in terms of the alkyl chain length of peculiar QAB. The effect of amino acids on CP of the drug solution is dependent upon the characteristics (acidic, basic, polar or nonpolar) of particular amino acids. The overall behavior of additives has been analyzed and discussed on the basis of electrostatic repulsion or interaction, micellar growth, and mixed micelle formation between the ingredients. In addition to this, thermodynamic parameters are also evaluated. [ABSTRACT FROM AUTHOR]

Purpose: Amitriptyline is the most widely used tricyclic antidepressant (TCA). Although amitriptyline hydrochloride 10 and 25 mg has been marketed in Korea, no data on the dose proportionality of amitriptyline in Korean subjects are available. This clinical trial was designed to evaluate and compare the relative bioavailability with regard to dose proportionality between the two marketed strengths of amitriptyline hydrochloride tablets after a single-dose, oral administration under fasting conditions in healthy, male, Korean volunteers. Methods: This single-dose, randomized, open-label, 2-way crossover study was conducted in healthy male Korean subjects. Subjects were randomly assigned to 1 of 2 dose groups and received a single dose of 10 or 25 mg amitriptyline hydrochloride under fasting conditions, followed by the alternate dose in the subsequent study period. High performance liquid chromatography (HPLC)-mass spectrometry (MS)/ MS detection was applied to determine plasma concentrations. Pharmacokinetic parameters were calculated, Cmax, AUClast, AUC0-∞, t½, and Tmax. Statistical analysis was performed for the assessment of dose proportionality. Tolerability was assessed for up to 96 hours after administration. Findings: Twelve healthy Korean subjects completed this trial (mean [SD] age, 21.7 [1.9] years; height, 174.5 [5.0] cm; and weight, 66.7 [9.4] kg). Although 4 subjects experienced a total 5 adverse events (AEs), no serious AEs were reported during the study. The mean values of Cmax and AUC were proportional to the doses of 10 and 25 mg. The Cmax, AUClast, and AUC0-∞ of amitriptyline hydrochloride 10 mg were 5.96 ng/mL, 91.35 ng . h/mL and 109.74 ng . h/mL, respectively. The Cmax, AUClast, and AUC0-∞ of amitriptyline hydrochloride 25 mg were 17.69 ng/mL, 260.68 ng . h/mL, and 296.87 ng . h/ mL, respectively. Implications: Our results suggest that the 2 strengths of amitriptyline hydrochloride (10 and 25 mg) exhibited linear (dose-dependent) pharmacokinetics in these healthy, male, Korean subjects. Based on these results, a predictable and linear increase in systemic exposure can be expected. [ABSTRACT FROM AUTHOR]

Abstract: In this paper we have reported the effect of two amphiphilic drugs, i.e., amitriptyline hydrochloride (AMT) and promethazine hydrochloride (PMT), on the cloud point (T CP) of hydroxypropylmethyl cellulose (HPMC) in the absence and presence of electrolytes. T CP of HPMC increased on increasing the [drug] and both drugs behaved almost in a same manner. In the presence of a small amount of NaCl (0.01molkg−1) T CP of the drug–polymer system showed a slight increase with a similar pattern as observed in its absence. The pattern of TCP change was different in the presence of high concentrations of NaCl (0.1 and 0.2molkg−1) which displayed a minimum in [drug] vs. TCP plots while the steepness and appearance of minimum depend upon the electrolyte concentration. The effect of other monovalent salts (NaBr, KCl, KBr) was also seen and it was noted that bromide and sodium ions were found to be more effective as compared to chloride and potassium ions, respectively, for affecting the T CP of HPMC. The energetics of the cloud point have been calculated and discussed. [Copyright &y& Elsevier]

• Micellization of amitriptyline hydrochloride (AMT) and TX-45 mixture were studied. • Clint, Rubingh, and Rosen models were applied to analyse the results. • Results suggest effective participation of TX-45 in mixed micelles of AMT + TX-45. • Salt enhances the micellization/surface activity whereas urea lessens the activity. • UV–Visible/FTIR were also conducted to extract information on components interaction. In this work, the surface and micellization behavior of amitriptyline hydrochloride (AMT) and a triton X-45 (TX-45) surfactant were studied in detail by surface tension measurement in the presence of simple salt NaCl and urea at 298.15 K. The mixtures of amphiphiles were analyzed by varying their compositions. The critical micelle concentration (cmc and cmc*), activity coefficients, interaction parameters, minimum area per molecule, interfacial adsorption, packing parameter (P), and various thermodynamic parameters for AMT + TX-45 mixtures with and without NaCl and urea at 298.15 K have been determined. Clint's, Rubingh's, and Maeda's models were used to analyze the results. The findings indicate attractive interactions in the AMT and non-ionic TX-45 mixture and suggest effective participation of the TX-45 when mixtures are employed in the absence and presence of additives. The average micellar composition of surfactant (X 1 Ru) , along with mixed monolayer composition of TX-45 (X 1 σ) value, in every solvent used contained over 70% TX-45, demonstrating that mixed mixed micelles and mixed monolayers contain much more TX-45 than AMT. In general, NaCl enhanced the micellization and surface activity, whereas urea lessened the activity of the studied system. UV–visible and Fourier transform infrared (FTIR) spectroscopy were also used to extract information on the interaction of AMT and TX-45 in aqueous solution. The current study aims to use TX-45 as an efficacious drug delivery vehicle for antidepressant drugs. [ABSTRACT FROM AUTHOR]

A simple CE method was developed and validated for the simultaneous determination of chlordiazepoxide (CHL), amitriptyline, and nortriptyline (mixture I) or the determination of CHL and imipramine (mixture II) using the same BGE. Sertraline and amitriptyline were used as internal standards for the first and second mixtures, respectively. The method allows amitriptyline to be completely separated from its impurity and main metabolite nortriptyline, which can be quantified from 0.2 μg/mL. The separation was achieved using 20 mM potassium phosphate buffer pH 5 containing 12 mM β-cyclodextrin and 1 mM carboxymethyl-β-cyclodextrin. UV detection was performed at 200 nm and a voltage of 15 kV was applied on an uncoated fused-silica capillary at 25°C. These experimental conditions allowed separation of the compounds to be obtained in 7 min. Calibration graphs proved the linearity up to 40 μg/mL for CHL, up to 100 μg/mL for amitriptyline and imipramine, and up to 5 μg/mL for nortriptyline. The accuracy and precision of the method have been determined by analyzing synthetic mixtures and pharmaceutical formulations. The analytical results were quite good in all cases indicating that the method was linear, sensitive, precise, accurate, and selective for both mixtures. [ABSTRACT FROM AUTHOR]

Pyrene fluorescence measurements were carried out on various binary mixtures of the antidepressant amphiphilic drug amitriptyline hydrochloride (AMT) with conventional (TTAB and CTAB) and gemini surfactants (14-4-14 and 16-4-16). In all cases mixed micellar aggregates were formed and the mixed critical micelle concentration ( cmc) of various mixtures was computed from the I/ I versus total surfactant concentration plots. In the region where mixed micelles are formed, the interaction of the amphiphlic drug and four surfactants showed synergistic behavior. The results were analyzed using an interaction parameter, β, which characterize the interaction in the mixed micelle and is introduced by a regular solution theory. The β values are negative in all binary mixtures, and their magnitudes increase with increasing hydrophobicity of the amphiphile. The micellar mole fraction of AMT in the mixed micelle ( x) and in the ideal sate ( x) were evaluated and their values ( x > x) suggest that the contribution of the AMT component is greater in binary mixtures as compared to that in the ideal state. Activity coefficients ( f and f) and excess Gibbs energy ( G) were also calculated. The values of micelle aggregation numbers ( N) and various other parameters like the Stern-Volmer constant ( K), micropolarity and dielectric constant of mixed systems have also been evaluated from the ratios of respective peak intensities ( I/ I or I/ I). [ABSTRACT FROM AUTHOR]

Transfer of four rapid thin-layer chromatography (TLC) screening methods used to detect substandard and fake pharmaceutical products to quantitative high-performance TLC (HPTLC)-densitometry methods is demonstrated using an expanded version of a model procedure that was published earlier. These methods for mebendazole, diphenhydramine hydrochloride, amodiaquine, and artesunate are contained in a Compendium of methods by Kenyon and Layloff and/or Minilab method manuals from Global Pharma Health Fund E.V. for use in countries with limited resources. A new HPTLC-densitometry method was also developed for amitriptyline hydrochloride, for which there was no Compendium or Minilab method that could be transferred. These quantitative methods use Merck HPTLC silica gel 60 F254glass plates, automated standard and sample solution application, and automated densitometry for detection, identification, and quantification. Standard and sample solution preparation and application procedures for obtaining calibration curves and bracketed samples are described. Additions to the previous model procedure include peak identity and purity checks by spectral comparison. HPTLC gives better efficiency, selectivity, and resolution than TLC, and the new methods overcome the deficiencies in technology related to manual application and visual zone comparison that do not allow the Compendium and Minilab TLC procedures to support regulatory compliance actions. These new methods can be fully validated according to International Conference on Harmonization (ICH) guidelines or by interlaboratory studies if their applications require. [ABSTRACT FROM AUTHOR]

Abstract: A new series of cationic surface active ionic liquids (SAILs) based on DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) was synthesized through the quaternization of DBU by alkyl bromides. The SAILs viz. DBU-C12 (8-N-dodecyl-1,8-diazabicyclo[5.4.0]undec-7-en-8-ium bromide), DBU-C14 (8-N-tetradecyl-1,8-diazabicyclo[5.4.0]undec-7-en-8-ium bromide) and DBU-C16 (8-N-hexadecyl-1,8-diazabicyclo[5.4.0]undec-7-en-8-ium bromide) were obtained and their aggregation behaviour was examined by surface tension and conductivity measurements. The SAILs investigated displayed better surface activity than the imidazolium based SAILs (CnmimBr) as well as the conventional cationic surfactants, alkyltrimethylammonium bromides (C n TAB). They also showed a decrease in critical micelle concentration (cmc) values with an increase in the alkyl chain length. Further, their interactions with amphiphilic drug, amitriptyline hydrochloride (AMT) have also been studied by employing the theoretical models proposed by Rubingh, Motomura and Gibbs. The micellar interaction parameter (β m ) is negative for most of the mole fractions of AMT (α AMT) in DBU-C14/DBU-C16 +AMT systems, indicating attractive interactions. The interfacial parameters such as surface tension reduction efficiency (pC 20), effectiveness of surface tension reduction (π cmc ), maximum surface excess concentration at the air-water interface (Γ max ) and minimum area per surfactant molecule (A min ) were also evaluated for the mixed systems of DBU based SAILs with AMT. The standard Gibbs free energy of micellization (ΔG° m ) and the standard free energy of adsorption at the air/water interface (ΔG°ad) for these systems were found to be negative, confirming the feasibility of these drug–SAIL interactions. [Copyright &y& Elsevier]

The effect of various organic additives, viz. sugars, ureas, alcohols, hydrotropes and bile salts on the clouding (phase separation) phenomenon of the amphiphilic antidepressant drug amitriptyline hydrochloride was investigated in the present study. All sugars lowered the cloud point (CP) due to their water structure-making property. Urea and alkylureas were found to lower the CP. In contrast, thioureas increased the CP slightly, but the presence of methyl group(s) had a similar effect in alkylureas. Short chain alcohols affected the CP insignificantly while higher ones decreased it, and medium chain alcohols showed peak behavior. Addition of hydrotropes and bile salts increased the CP at lower concentrations, while a decrease was observed at higher concentrations (like the medium chain alcohols). In addition, thermodynamic parameters were also evaluated but only for those additives which formed mixed micelles with the drug. [ABSTRACT FROM AUTHOR]