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Abstract Effective drugs for the treatment of gastric cancer (GC) are still lacking. Nortriptyline Hydrochloride (NTP), a commonly used antidepressant medication, has been demonstrated by numerous studies to have antitumor effects. This study first validated the ability of NTP to inhibit GC and preliminarily explored its underlying mechanism. To begin with, NTP inhibits the activity of AGS and HGC27 cells (Human-derived GC cells) in a dose-dependent manner, as well as proliferation, cell cycle, and migration. Moreover, NTP induces cell apoptosis by upregulating BAX, BAD, and c-PARP and downregulating PARP and Bcl-2 expression. Furthermore, the mechanism of cell death caused by NTP is closely related to oxidative stress. NTP increases intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, decreasing the mitochondrial membrane potential (MMP) and inducing glucose (GSH) consumption. While the death of GC cells can be partially rescued by ROS inhibitor N-acetylcysteine (NAC). Mechanistically, NTP activates the Kelch-like ECH-associated protein (Keap1)—NF-E2-related factor 2 (Nrf2) pathway, which is an important pathway involved in oxidative stress. RNA sequencing and proteomics analysis further revealed molecular changes at the mRNA and protein levels and provided potential targets and pathways through differential gene expression analysis. In addition, NTP can inhibited tumor growth in nude mouse subcutaneous tumor models constructed respectively using AGS and MFC (mouse-derived GC cells), providing preliminary evidence of its effectiveness in vivo. In conclusion, our study demonstrated that NTP exhibits significant anti-GC activity and is anticipated to be a candidate for drug repurposing.

In this study, the electrical conductivity of the antidepressant drug—nortriptyline hydrochloride and conventional surfactant—cetyldimethylethylammoniumbromide are investigated. The experimental critical micelle concentration and related thermodynamic parameters, such as Gibbs free energy, enthalpy, entropy change, as well as and excess change in Gibbs free energy are calculated using standard equations. The values of change in Gibbs free energy for the mixed nortriptyline hydrochloride with cetyldimethylethylammoniumbromide are found to be more negative further suggesting the mixed micellization to be favourable. However, the high values of change in entropy are observed owing to the charge on the head groups which are being partially neutralized by the counter ions upon micelle formation. [ABSTRACT FROM AUTHOR]

Cyclodextrin-based delivery systems have been intensively used to improve the bioavailability of drugs through the modification of their pharmaceutically relevant properties, such as solubility, distribution and membrane permeation. The present work aimed to disclose the influence of HP-β-CD and SBE-β-CD on the distribution and permeability of nortriptyline hydrochloride (NTT•HCl), a tricyclic antidepressant drug. To this end, the distribution coefficients in the 1-octanol/buffer and n-hexane/buffer model systems and the coefficients of permeability through the cellulose membrane and lipophilic PermeaPad barrier were determined at several cyclodextrin concentrations. The results demonstrated a dramatic decrease in both the distribution and the permeability coefficients as the cyclodextrin concentration rose, with the decrease being more pronounced in SBE-β-CD due to the charge–charge attraction and electrostatic interactions between NTT and SBE-β-CD. It is these interactions that were shown to be responsible for the greater value of the constant of NTT's association with SBE-β-CD than that with HP-β-CD. The findings of this study revealed similar trends in the 1-octanol/buffer 6.8 pH distribution and permeability through the PermeaPad barrier in the presence of CDs. These results were attributed to the determinative role of the distribution coefficient (serving as a descriptor) in permeation through the PermeaPad barrier modeling the lipophilic nature of biological barriers. [ABSTRACT FROM AUTHOR]

Some of the most commonly used analgesic drugs in animals are of questionable efficacy or present adverse side effects among the various species of reptiles. Tricyclic antidepressants have been demonstrated to have antinociceptive effects in several animal models of pain and could be a good alternative for use in reptiles. The aim of the study was to investigate the antinociceptive effects of nortriptyline and desipramine hydrochloride in Speke's hinge‐back tortoise. A total of 24 animals weighing 600–1000 g were used for nociceptive tests, i.e., formalin, capsaicin, and hot plate tests. Drugs were administered intracoelomically 30 min before starting the tests. The time spent in nocifensive behavior and the associated observable effects during the tests were recorded. Only the highest dose of 40 mg/kg of nortriptyline hydrochloride caused statistically significant decrease in nocifensive behavior in both the formalin and the capsaicin test. Desipramine hydrochloride at doses of 20 and 40 mg/kg caused statistically significant decrease in nocifensive behavior in the formalin test. Also, desipramine hydrochloride at doses of 15, 20, and 60 mg/kg caused statistically significant decrease in nocifensive behavior in the capsaicin test. None of the doses used for both drugs had any statistically significant effect on nocifensive behavior in the hot plate test. The results show that nortriptyline and desipramine hydrochloride have significant antinociceptive effects in the chemical but not thermal inflammatory pain‐related behavior in the Speke's hinge‐back tortoise. The most common associated side effect following administration of the higher doses of either of the drugs is excessive salivation. [ABSTRACT FROM AUTHOR]

Cyclodextrin-based delivery systems have been intensively used to improve the bioavailability of drugs through the modification of their pharmaceutically relevant properties, such as solubility, distribution and membrane permeation. The present work aimed to disclose the influence of HP-β-CD and SBE-β-CD on the distribution and permeability of nortriptyline hydrochloride (NTT•HCl), a tricyclic antidepressant drug. To this end, the distribution coefficients in the 1-octanol/buffer and n-hexane/buffer model systems and the coefficients of permeability through the cellulose membrane and lipophilic PermeaPad barrier were determined at several cyclodextrin concentrations. The results demonstrated a dramatic decrease in both the distribution and the permeability coefficients as the cyclodextrin concentration rose, with the decrease being more pronounced in SBE-β-CD due to the charge–charge attraction and electrostatic interactions between NTT and SBE-β-CD. It is these interactions that were shown to be responsible for the greater value of the constant of NTT’s association with SBE-β-CD than that with HP-β-CD. The findings of this study revealed similar trends in the 1-octanol/buffer 6.8 pH distribution and permeability through the PermeaPad barrier in the presence of CDs. These results were attributed to the determinative role of the distribution coefficient (serving as a descriptor) in permeation through the PermeaPad barrier modeling the lipophilic nature of biological barriers.

The present work reports a validated reverse phase-HPLC method for determination of nortriptyline hydrochloride (NORH) in bulk and in its pharmaceutical dosage form. Chromatographic separation was performed on Waters C-18, (250×4.6mm, 5µm) stationary phase using a mixture of 50 mM KH2 PO4 pH 3.0 phosphate buffer: methanol: acetonitrile in the proportion of 50: 10: 40 V/V/V as mobile phase components at 1.0 mL min-1 flow rate. Detection of drug was carried out in isocratic mode at 235 nm. The validation of the method was carried out as per ICH guidelines. The LOD and LOQ for NORH was 0.22 µg mL-1 and 0.69 µg mL-1, respectively. NORH showed linearity range of 5-50 µg mL-1 and correlation coefficient (r² ) value, 0.9937. The method was tested for assay of NORH in tablet dosage form. [ABSTRACT FROM AUTHOR]

A Simple, rapid, specific, accurate, economical and precise UV spectrophotometric and RP-HPLC methods (in accordance with ICH guidelines) were developed and validated for determination of Nortriptyline hydrochloride and Pregabalin in tablet dosage form. The first method was based on Q - absorbance ratio, and absorbances of both drugs were determined at 239 nm (λmax of Nortriptyline Hydrochloride) and 235 nm (Iso-absorptive Point) when dissolved in methanol. It is found that Pregabalin does not have chromophoric group. To be UV-sensitive, it was compulsory to introduce chromophoric group in Pregabalin structure and make it UV-sensitive. This was achieved by converting the primary amine group of Pregabalin through reaction with benzoyl chloride to form benzoylated derivative of Pregabalin. Benzoylated Pregabalin was determined at 225 nm using UV-visible spectrophotometer. The second method was based on RP-HPLC. The chromatographic separation was performed on an Inertsil ODS C18 column (250 x 4.6mmx 5 μm) with a mobile phase of 0.56 %w/v Sodium hexane sulphonic acid dissolved in water acetonitrile (50:50 %v/v, pH 4.5 adjusted with Glacial Acetic Acid) at flow rate of 1.0 mL/min with DAD detection wavelength at 210 nm. Retention times of Nortriptyline Hydrochloride and Pregabalin were 7.3894 min and 4.0506 min, respectively. Beer-Lambert's law obeyed the concentration range of 2-12 μg/mL for Nortriptyline Hydrochloride and 10-60 μg/mL for Pregabalin. The results indicated that both spectrophotometric and RP-HPLC methods were linear, accurate, precise and robust with RSD values less than 0.2% and % recovery was within the standard limits (99 - 102%). [ABSTRACT FROM AUTHOR]

The simple, precise and accurate UV-Spectrophotometric method has been developed and validated for the estimation of nortriptyline hydrochloride in bulk and dosage form. In that work was carried out for estimation of nortriptyline hydrochloride in bulk and pharmaceutical dosage form by utilizing area under curve (AUC) method. For this purpose the wavelength range 200-400nm was selected. DMSO was used as solvent throughout the work. Linearity was observed in concentration range 5-25µg/ml (R² =0.996) for the method. The present method was found which can be used for routine quality control analysis for spectrophotometric estimation of Nortriptyline hydrochloride in bulk and dosage form. [ABSTRACT FROM AUTHOR]

Highlights • (V ∅ 0) and (K ∅ , s 0) values indicate strong solute-solvent interactions in mixtures. • ∂ 2 V ∅ 0 / ∂ 2 T P predict amino acids as structure-breaker in aqueous NTPH solutions. • Positive hydration number suggests strong dehydration effect of NTPH. • Positive V AB and K AB values show pairwise interaction between amino acids and NTPH. • FTIR data indicate greater solvation in the mixtures of amino acids and NTPH. Abstract Apparent and partial molar properties for glycine, L -alanine and L -valine in aqueous solutions (0.025–0.075) mol·kg−1 of drug NTPH (nortriptyline hydrochloride) have been reported in the present study at intervals of 5 K from temperature 288.15 K to 308.15 K and at experimental pressure of p = 0.1 MPa. Different parameters viz. transfer partial molar properties, hydration numbers (n H) , partial molar expansibility (E ∅ 0) , isobaric thermal expansion coefficient (α) and Hepler's constant, calculated by using the experimental data of density (ρ) and ultrasonic speeds (u) predict that the solute-solvent interactions are dominating in these ternary systems. The linear variation of V ∅ 0 with the number of carbon atoms in the alkyl chain of amino acids has been utilized to calculate the contribution of the charged end groups NH 3 + , C O O - , (C H 2) group and other alkyl chains of the amino acids to V ∅ 0. Pair and triplet interaction coefficients determined from Δ V ∅ 0 and Δ K ∅ , s 0 values using McMillan-Mayer theory indicate the dominance of pairwise interactions in the studied ternary mixtures. The hydration number (n H) comes out to be positive suggesting strong dehydration effect of NTPH. FTIR spectra have been recorded for the mixtures of amino acids in aqueous solutions of NTPH. The decrease in wave number of N–H stretching band also suggests the structural changes in these systems. [ABSTRACT FROM AUTHOR]

The interaction of the antidepressant drug nortriptyline hydrochloride (NOT) with the surface-active ionic liquid (SAIL), 1-decyl-3-methylimidazolium chloride, [C10mim][Cl], has been studied using multiple techniques, including conductometric titration, tensiometric, fluorometric, dynamic light scattering and UV-visible spectrophotometric measurements. There is a significant decrease in the cmc of SAIL on the addition of the drug NOT, indicating adsorption of drug molecules in the outer portion of the micelle. In the present study, the values of the packing parameter, P, lie in the range of 0-0.3, which suggests that the micelles formed are spherical in nature. More negative values of the standard Gibbs energy of adsorption, ΔGad∘, compared to ΔGm∘ support our contention that adsorption of SAIL on the air-solution interface is relatively more favorable than its micellization in the presence of NOT. Fluorescence and DLS studies indicate that the aggregation number, Nagg, and hydrodynamic radius of SAIL increase with increase in concentration of NOT. The UV-visible spectroscopic study confirms the formation of a new complex between SAIL and NOT; this is also supported by the negative Gibbs energy of complexation. [ABSTRACT FROM AUTHOR]

This paper deals with a comprehensive study of the mixed micellization and adsorption behavior of mixed systems enclosing an amphiphilic antidepressant drug nortriptyline hydrochloride (NOT) and Triton X-114 (TX-114) (nonionic surfactant) in aqueous/urea (500 mmol·kg−1 and 1000 mmol·kg−1) solutions by tensiometric method. The NOT is used for the cure of depression. For comparison purpose cmc value of pure drug NOT was also evaluated by conductimetric technique. Different theoretical models like Clint, Rubingh, and Rosen were used to get information about the nature of interaction between the components in bulk and at the interface. Because of the occurrence of urea increase in the surface charge of the micelles was obtained resulting a delay of the micelles formation. The cmc values of the mixed systems of NOT and TX-114 were found to be in between the cmc values of pure components, which signify nonideal mixed system having attractive interactions in the absence and presence of urea. Various parameters such as micellar mole fractions of TX-114 ( X1m, X1σ) in solution and at interface, interaction parameter ( βm/ βσ) in solution and at interface, and activity coefficient in solution and at interface were evaluated and discussed using Rubingh's and Rosen's models. Surface excess ( Γmax) increases that means minimum area per head group ( Amin) decreases as mole fraction ( α1) of TX-114 increases in the absence/presence of urea. Different thermodynamic parameters have been calculated and discussed. The ∆ G0m values achieved are all negative both in the absence and occurrence of urea. [ABSTRACT FROM AUTHOR]

The aggregation and interfacial behavior of two Gemini surfactants ethylene-1, 2-bis (N, N-dimethyl-N-tetradecylammonium bromide) (14-2-14) and ethylene-1, 2-bis (N, N-dimethyl-N-dodecylammonium bromide) (12-2-12) have been scrutinized in absence and presence of antidepressant drug Nortriptyline Hydrochloride (NH) having concentrations (0.10, 0.15 and 0.25) mmol/kg through surface tension measurements at 298.15 K and via conductivity measurements at 293.15, 298.15, 303.15 and 308.15 K. Various surface active parameters such as minimum surface area per surfactant molecule (A min), surface tension at CMC (γ cmc), maximum surface excess concentration (Γ max), surface pressure (ᴨ cmc), and CMC of the studied systems of surfactants and NH have been determined from surface tension measurements. Different parameters like degree of ionization (α) inclusive of CMC and thermodynamic parameters of micellization like standard enthalpy of micellization (Δ H m 0 ), standard entropy of micellization (Δ S m 0 ) and Gibbs free energy of micellization (Δ G m 0 ) have been attained using conductivity measurements. Since these Gemini surfactants have improved surface activity in comparison to monomeric conventional surfactants, they can enhance permeability of drugs through bio membranes which make them better drug carriers in contrast to prevailing solutions. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Physico-chemical properties of glycine and its peptides in aqueous NTPH solutions. • Dominance of solute-solvent interactions indicated by apparent molar properties. • Volume and compression data suggest the dominance of ion-hydrophilic and hydrophilic-hydrophilic interactions. • Positive values of pair interaction coefficients predict pair wise interaction. • Amino acid/peptide behaves as a structure breaker in water and in aqueous nortriptyline hydrochloride solutions. From the density (ρ), speed of sound (u) and viscosity (η) measurements, the interactions of glycine, glycylglycine and glycylglycylglycine with antidepressant drug, nortriptyline hydrochloride have been investigated in aqueous medium at temperatures, T = (293.15–313.15) K and experimental pressure p = 0.1 MPa. From the experimental density measurements, apparent molar volume (V Φ), limiting apparent molar volume ( V o Φ) and partial molar volumes of transfer ( V o Φ , t r ) have been determined for various solutions of glycine, glycylglycine and glycylglycylglycine in aqueous nortriptyline hydrochloride. In addition, using speed of sound data, apparent molar isentropic compression (K s , Φ ), limiting apparent molar isentropic compression ( K o s , Φ ) and partial molar isentropic compression of transfer ( K o s , Φ , t r ) have been calculated. Pair and triplet interaction coefficients are also determined from V o Φ , t r values using McMillan-Mayer theory. Further, apparent molar expansibility ( E o Φ) and Hepler's constant values ∂ E o Φ ∂ T P have been evaluated to assist the interpretations earned from the volumetric and acoustic analysis. The viscosity coefficients A and B , viscosity B -coefficient of transfer (B tr ) and temperature derivative of B -coefficients (dB / dT) have been determined from viscosity data. The results were interpreted in terms of different kinds of intermolecular interactions present in the ternary systems (amino acid/peptides + water + nortriptyline hydrochloride) through a cosphere overlap model. The Hepler's constant and temperature derivative of B -coefficients (dB / dT) confirms the structure breaking nature of the solute. [ABSTRACT FROM AUTHOR]

Abstract: A novel method for the simultaneous high-performance liquid chromatographic determination of nortriptyline hydrochloride and fluphenazine hydrochloride was developed and validated. Fluvastatin sodium was used as internal standard. The determination was performed on a Hypersil Gold C8 column (250 mm × 4.6 mm i.d., 5μm particle size) at 25°C; the mobile phase, consisting of a mixture of formic acid (0.1M, pH 2.16)-methanol (33:67, v/v), was delivered at a flow rate of 1.1mL/min and detector wavelength at 251nm. The retention time of nortriptyline, fluphenazine and fluvastatin was found to be 5.11, 8.05 and 11.38min, respectively. Linearity ranges were 5.0–1350.0 and 10.0–1350.0μg/mL with limit of detection values of 0.72 and 0.31μg/mL, for nortriptyline and fluphenazine, respectively. Results of assay and recovery studies were statistically evaluated for its accuracy and precision. Correlation coefficients (r 2) of the regression equations were greater than 0.999 in all cases. According to the validation results, the proposed method was found to be specific, accurate, precise and could be applied to the simultaneous quantitative analysis of nortriptyline and fluphenazine. [Copyright &y& Elsevier]

A surface tension study was performed on mixed amphiphilic drug-nonionic surfactant systems. The drugs used were adiphenine hydrochloride and nortriptyline hydrochloride whereas surfactants were ethoxylated sorbitan esters and polyethylene oxide-polypropylene oxide-polyethylene oxide triblocks. The critical micelle concentration (CMC) and CMC (CMC at ideal mixing condition) values suggest nonideal and attractive interactions among the components. The micellar mole fraction $$ (X_{ 1}^{\text{m}} ) $$ values calculated using Rubingh's model indicate predominance of the nonionic surfactant in micelle formation. The mole fraction of surfactant in mixed monolayer $$ (X_{1}^{\sigma } ) $$ values are greater than $$ X_{ 1}^{\text{m}} $$ values, indicating a greater contribution of surfactant in monolayer formation. Thermodynamic parameters, viz. Gibbs energy of micellization $$ (\Updelta G_{\text{m}}^{\text{o}} ) $$, Gibbs energy of adsorption $$ (\Updelta G_{\text{ad}}^{\text{o}} ) $$, and excess free energy of mixed micelles $$ (\Updelta G_{\text{ex}}^{\text{m}} ) $$ and monolayers $$ (\Updelta G_{\text{ex}}^{\sigma } ) $$ were also evaluated. All these values suggest stable mixed micelle and mixed monolayer formation. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to prepare and characterize both physically and biopharmaceutically, a nortriptyline hydrochloride (NTP-HCl) patch formulated in chitosan. Methods: 16 g of each chitosan patch formulation (I, II and III, see Table 1) was poured onto rectangular glass plates (64 cm2) at a height of 1 mm and dried for 24 h at room temperature. In order to characterize the chitosan patches, polarized microscopy, in vitro skin permeation studies by passive diffusion and iontophoresis and rheological and bioadhesion studies were performed. Results: Polarized microscopy revealed the absence of aggregates and crystal forms of NTP-HCl in all transdermal patches after 30 days of storage. The rheological behavior of Patches I, II and III was predominantly elastic. The low level of adhesion of Patch III (containing PF-127 ++ 1-dodecanol) could be a result of the interactions between chitosan and PF-127 in the presence of 1-dodecanol. Patches I and II had approximately the same value of adhesion (≈≈ 60 mN.mm). The transdermal patch with chitosan, PF-127 and 1-dodecanol (Patch III) provided a reasonable flux of NTP-HCl across the skin compared with Patches I and II. Iontophoresis applied to the patches did not increase the penetration of NTP-HCl across the skin. Conclusions: The data suggest that Patch III is suitable for use in clinical practice pending further studies. [ABSTRACT FROM AUTHOR]

Abstract: The objective of this work was to develop a simple and inexpensive transdermal formulation containing Nortriptyline Hydrochloride (NTH) for smoking cessation support therapy. Hydroxypropyl-methyl-cellulose was chosen as polymer and a mixture of transdermal enhancers (selected from previous research) was incorporated. The formulations were characterised in terms of appearance, thickness, uniformity of NTH content, release and skin permeation. Release studies demonstrated controlled release for four formulations. Diffusion studies were performed through human heat separated epidermis (HHSE) using Franz Diffusion Cells (FDC). Patches provided different fluxes varying from 20.39±7.09μg/(cm2 h) to 256.19±94.62μg/(cm2 h). The penetration profiles of NTH within the stratum corneum (SC) and deeper skin layers (DSL) were established after three administration periods (3h, 6h, and 24h). Skin changes induced by the application of the patches were observed by confocal laser scanning microscopy (CLSM). The highest flux obtained would provide the recommended doses for smoke cessation support therapy (25–75mg per day) with a 2cm×2cm patch or a 3.5cm×3.5cm patch, respectively, without skin damage evidence. [Copyright &y& Elsevier]

The cloud point (CP) phenomenon has been studied in amphiphilic drug nortriptyline hydrochloride solutions with or without additives. The drug solutions were prepared in 10 mM sodium phosphate buffer. An increase in pH decreases the solution CP in the absence as well as the presence of additives (urea and TBuAB) due to deprotonation of the drug molecules. At constant pH (7.07), addition of simple salts (NaF, NaCl, NaBr) increases the CP by increasing the micelle hydration. Addition of Br salts (LiBr, NaBr, KBr) also increases the CP. The behavior is explained on the basis of the cation hydrated radius. Quaternary ammonium bromides, due to adsorption/mixed-micelle formation, also increase the CP, the order being: BuC = O or >C = S moiety. The former interacts with the micelles and decreases CP while the latter (due to its electropositive character) may not interact and hence increases CP. [ABSTRACT FROM AUTHOR]

Spectrophotometric and high performance liquid chromatographic procedures are described for determination of nortriptyline hydrochloride and fluphenazine hydrochloride. The first procedure is based on application of first derivative of ratio spectra (¹DD) for quantitative determination of nortriptyline hydrochloride in presence of fluphenazine hydrochloride. Secondly, an accurate, sensitive and stability indicating method has been introduced for determination of nortriptyline hydrochloride and fluphenazine hydrochloride in both bulk powder and in dosage form. In the derivative ratio method, Beer's law is obeyed in the concentration ranges of 8-32 µg mL[sup -1] and 4-32 µg mL[sup -1] of nortriptyline hydrochloride at wavelengths 271.4 and 284.2 nm, respectively. In high performance liquid chromatographic method, linear relationship in the range of 0.6-3.6 µg mL[sup -1] and 1.2-4.2 µg mL[sup -1] for nortriptyline hydrochloride and fluphenazine hydrochloride, respectively, was obtained. The mobile phase used was 0.05 M ammonium acetate: methanol: acetonitrile (4:1:5 v/v/v), and detection was done spectrophotometrically at 254 nm. Results were statistically analyzed and compared with those obtained by applying the British Pharmacopoeia (2000) method. [ABSTRACT FROM AUTHOR]

The solubility of a model basic drug, nortriptyline (Nor), was investigated as a function of pH in phosphate and/or a chloride-containing aqueous suspension using experimental practices recommended in the previously published "white paper" (Avdeef et al., 2016). The pH-Ramp Shake-Flask (pH-RSF) method, introduced in our earlier work (Marković et al., 2019), was applied. An improved and more detailed experimental design of the Nor solubility measurement allowed us to exploit the full capacity of the pH-RSF method. Complex equilibria in the aqueous phase (cationic and anionic complex formation between Nor and the phosphate) and solid-phase transformations (Nor free base, 1:1 Nor hydrochloride salt, 1:1 and 1:2 Nor phosphate salts) were characterized by a detailed analysis of the solubility measurements using the computer program p DISOL-X. The solid phases were characterized by thermogravimetric analysis, differential scanning calorimetry, powder X-ray diffraction, and elemental analyses. The results of the present investigation illustrate the influence of competing counterions, such as buffering agents, complexing agents, salt coformers, tonicity adjusters, and so forth, on the aqueous solubility of drugs and interconversion of salts. Careful attention given to these factors can be helpful in the formulation of drug products.

Abstract: Six different matrices were prepared containing nortriptyline hydrochloride (NTH) with hydroxypropyl-methyl-cellulose as polymer. A mixture of transdermal enhancers was included as part of the vehicle. Diffusion studies were carried out through Wistar rat full thickness skin using Franz cells. They were compared with previously determined human heat separated epidermis in order to test if this animal can be used as model for in vivo assays. A linear correlation was obtained between NTH diffusion coefficients through both skin types (r 2 =0.996). [Copyright &y& Elsevier]