Procaine HCl Research Articles

Profiling skin penetration using PEGylated emulsifiers as penetration enhancers via confocal Raman spectroscopy and fluorescence spectroscopy

Non-ionic emulsifiers have been continuous research focus in skin analysis. With the aim of finding their role as penetration enhancers in dermal drug delivery systems, PEGylated emulsifiers of polyethylene glycol (PEG) ethers were targeted to be investigated ex-vivo. The effectiveness of them in the enhancement of skin penetration was examined by conventional tape stripping method and confocal Raman spectroscopy (CRS). Fluorescein sodium salt (Fluo-Na) and procaine HCl were respectively used as model drugs. The drug delivery performances were compared in the aspects of penetration amount and depth. Based on the results from both analyses, all investigated emulsifiers have the ability to enhance the amount of drug penetration. PEG-20 ethers showed higher ability than PEG-2 oleyl ether (O2) in promoting drug distribution by depth, especially PEG-20 cetyl ether (C20) showed a distinct effect. According to this study, their penetration enhancing performances seem to be linked to their interruption of intercellular lipids, which can be considered as the underlying mechanism for governing the ability of PEGylated emulsifiers as penetration enhancers. Further instrumental comparison highlighted the benefits of using CRS as an alternative in skin penetration analysis.

Molecular dynamics in amorphous pharmaceutically important protic ionic liquid–benzalkonium chloride

In this paper, we report the dielectric measurements at ambient pressure to portray the molecular dynamics of a glass forming pharmaceutical as well as a protic ionic conductor, benzalkonium chloride [BaCl] by means of broadband dielectric spectroscopy. The measurement in macroscopic nature of a stochastic transport theory and of the electric modulus formalism stanchly reproduces the shape of the dispersion of the microscopic ionic movement in terms of translational and ionic diffusive motion of molecular ions. The situation is analogous to most ionic conductors, BaCl showed only single resolved peak in the electric modulus formalism and doesn't show any crystallisation tendency during cooling as well as heating. The temperature dependence of the conductivity relaxation has been fitted by single Vogel–Fulcher–Tamman (VFT) equation. It is found that the value of Tg observed from DSC is significantly higher than one obtained from the α-conductivity relaxation corresponding to 100s indicating that the structural τα(Τ) is longer than conductivity τσα(Τ) for about 10K. Finally, the results were compared with data for other protic ionic conductors like Procaine HCl, Procainamide HCl, Verapamile HCl, Lidocaine HCl, Tramadole HCl and Chlorpromazine HCl and found that BaCl is a good strong glass former.

How Confocal Is Confocal Raman Microspectroscopy on the Skin? Impact of Microscope Configuration and Sample Preparation on Penetration Depth Profiles

Background/Aims: The aim of the study was to elucidate the effect of sample preparation and microscope configuration on the results of confocal Raman microspectroscopic evaluation of the penetration of a pharmaceutical active into the skin (depth profiling). Methods: Pig ear skin and a hydrophilic formulation containing procaine HCl were used as a model system. The formulation was either left on the skin during the measurement, or was wiped off or washed off prior to the analysis. The microscope configuration was varied with respect to objectives and pinholes used. Results: Sample preparation and microscope configuration had a tremendous effect on the results of depth profiling. Regarding sample preparation, the best results could be observed when the formulation was washed off the skin prior to the analysis. Concerning microscope configuration, the use of a 40 × 0.6 numerical aperture (NA) objective in combination with a 25-µm pinhole or a 100 × 1.25 NA objective in combination with a 50-µm pinhole was found to be advantageous. Conclusion: Complete removal of the sample from the skin before the analysis was found to be crucial. A thorough analysis of the suitability of the chosen microscope configuration should be performed before acquiring concentration depth profiles.

Spectroscopic Studies on Host–Guest Interactions of α- and β-Cyclodextrin with Lidocaine Hydrochloride and Procaine Hydrochloride

Lidocaine HCl and procaine HCl are local anesthetics widely used in minor chirurgic procedures; nevertheless, spectral information about their behavior is not complete at present. In this context, in this paper, absorbance and fluorescence studies of both the drugs with α- and β-cyclodextrins (CDs) have been measured at 298.15 K. The thermodynamic parameters: binding constant (K) and standard state Gibbs energy (∆G°) were calculated for the systems in which complex formation was observed. The α- and β-CD study indicates that the lidocaine HCl and procaine HCl drugs form 1:1 inclusion complex with α- and β-CD. Both experimental and theoretical studies revealed that the phenyl ring with the amide group of the drug is encapsulated in the hydrophobic CD cavity. van der Waals interactions are mainly responsible for complex formation of lidocaine hydrochloride and procaine hydrochloride with CDs.

Decoupling of conductivity relaxation from structural relaxation in protic ionic liquids and general properties

The main focus of this work is the study of conductivity relaxation of amorphous lidocaine hemisuccinate near the glass transition at ambient pressure. Measurements have been made using broadband dielectric spectroscopy (BDS) and temperature-modulated differential scanning calorimetry. Our study shows that the ion conductivity relaxation becomes increasingly faster than the structural relaxation as the glass transition temperature Tg is approached. At Tg the structural relaxation time is longer than the conductivity relaxation times by three decades, i.e. the decoupling index Rτ is about 3. Decoupling is accompanied by the ion conductivity relaxation which narrows in its frequency dispersion with decreasing temperature. This abnormal behavior is identical to that found in two other protic ionic liquids (PILs), procaine HCl and procainamide HCl. Considering that the phenomenon has been found before in several inorganic ionic glass-formers and now in three protic ionic liquids, it could be a general property of ionically conducting glass-forming substances, although more cases have to be studied before a definitive conclusion can be made. We show that it can be rationalized within the framework of the Coupling Model.

Batch and Flow-Injection Spectrophotometric Determination of Procaine HCl in Pharmaceutical Preparations Via Using Diazotization and Coupling Reaction

Simple and sensitive batch and Flow-injection spectrophotometric methods for the determination of Procaine HCl in pure form and in injections were proposed. These methods were based on a diazotization reaction of procaine HCl with sodium nitrite and hydrochloric acid to form diazonium salt, which is coupled with chromatropic acid in alkaline medium to form an intense pink water-soluble dye that is stable and has a maximum absorption at 508 nm. A graphs of absorbance versus concentration show that Beer’s law is obeyed over the concentration range of 1-40 and 5-400 µg.ml-1 of Procaine HCl, with detection limits of 0.874 and 3.75 µg.ml-1 of Procaine HCl for batch and FIA methods respectively. The FIA average sample throughput was 70 h-1. All different chemical and physical experimental parameters that affecting on the development and stability of the colored product were carefully studied and the proposed methods were applied satisfactorily for the determination of Procaine HCl in an injections samples using the standard addition method.

Batch and Flow-Injection Spectrophotometric Determination of Procaine HCl in Pharmaceutical Preparations Via Using Diazotization and Coupling Reaction

Simple and sensitive batch and Flow-injection spectrophotometric methods for the determination of Procaine HCl in pure form and in injections were proposed. These methods were based on a diazotization reaction of procaine HCl with sodium nitrite and hydrochloric acid to form diazonium salt, which is coupled with chromatropic acid in alkaline medium to form an intense pink water-soluble dye that is stable and has a maximum absorption at 508 nm. A graphs of absorbance versus concentration show that Beer’s law is obeyed over the concentration range of 1-40 and 5-400 µg.ml-1 of Procaine HCl, with detection limits of 0.874 and 3.75 µg.ml-1 of Procaine HCl for batch and FIA methods respectively. The FIA average sample throughput was 70 h-1. All different chemical and physical experimental parameters that affecting on the development and stability of the colored product were carefully studied and the proposed methods were applied satisfactorily for the determination of Procaine HCl in an injections samples using the standard addition method.

Batch and Flow-Injection Spectrophotometric Determination of Thymol Using Procaine Hydrochloride as a New Chromogenic Reagent

New, simple and sensitive batch and Flow-injecton spectrophotometric methods for the determination of Thymol in pure form and in mouth wash preparations have been proposed in this study. These methods were based on a diazotization and coupling reaction between Thymol and diazotized procaine HCl in alkaline medium to form an intense orange-red water-soluble dye that is stable and has a maximum absorption at 474 nm. A graphs of absorbance versus concentration show that Beer’s law is obeyed over the concentration range of 0.4-4.8 and 4-80 µg.ml-1 of Thymol, with detection limits of 0.072 and 1.807 µg.ml-1 of Thymol for batch and FIA methods respectively. The FIA procedure sample throughput was 80 h-1. All different chemical and physical experimental parameters that affecting on the development and stability of the colored product were carefully studied and the proposed methods were successfully applied to the determination of Thymol in mouth wash preparations.

Batch and Flow-Injection Spectrophotometric Determination of Thymol Using Procaine Hydrochloride as a New Chromogenic Reagent

New, simple and sensitive batch and Flow-injecton spectrophotometric methods for the determination of Thymol in pure form and in mouth wash preparations have been proposed in this study. These methods were based on a diazotization and coupling reaction between Thymol and diazotized procaine HCl in alkaline medium to form an intense orange-red water-soluble dye that is stable and has a maximum absorption at 474 nm. A graphs of absorbance versus concentration show that Beer’s law is obeyed over the concentration range of 0.4-4.8 and 4-80 µg.ml-1 of Thymol, with detection limits of 0.072 and 1.807 µg.ml-1 of Thymol for batch and FIA methods respectively. The FIA procedure sample throughput was 80 h-1. All different chemical and physical experimental parameters that affecting on the development and stability of the colored product were carefully studied and the proposed methods were successfully applied to the determination of Thymol in mouth wash preparations.

Fundamentals of ionic conductivity relaxation gained from study of procaine hydrochloride and procainamide hydrochloride at ambient and elevated pressure

The pharmaceuticals, procaine hydrochloride and procainamide hydrochloride, are glass-forming as well as ionically conducting materials. We have made dielectric measurements at ambient and elevated pressures to characterize the dynamics of the ion conductivity relaxation in these pharmaceuticals, and calorimetric measurements for the structural relaxation. Perhaps due to their special chemical and physical structures, novel features are found in the ionic conductivity relaxation of these pharmaceuticals. Data of conductivity relaxation in most ionic conductors when represented by the electric loss modulus usually show a single resolved peak in the electric modulus loss M(")(f) spectra. However, in procaine hydrochloride and procainamide hydrochloride we find in addition another resolved loss peak at higher frequencies over a temperature range spanning across T(g). The situation is analogous to many non-ionic glass-formers showing the presence of the structural α-relaxation together with the Johari-Goldstein (JG) β-relaxation. Naturally the analogy leads us to name the slower and faster processes resolved in procaine hydrochloride and procainamide hydrochloride as the primary α-conductivity relaxation and the secondary β-conductivity relaxation, respectively. The analogy of the β-conductivity relaxation in procaine HCl and procainamide HCl with JG β-relaxation in non-ionic glass-formers goes further by the finding that the β-conductivity is strongly related to the α-conductivity relaxation at temperatures above and below T(g). At elevated pressure but compensated by raising temperature to maintain α-conductivity relaxation time constant, the data show invariance of the ratio between the β- and the α-conductivity relaxation times to changes of thermodynamic condition. This property indicates that the β-conductivity relaxation has fundamental importance and is indispensable as the precursor of the α-conductivity relaxation, analogous to the relation found between the Johari-Goldstein β-relaxation and the structural α-relaxation in non-ionic glass-forming systems. The novel features of the ionic conductivity relaxation are brought out by presenting the measurements in terms of the electric modulus or permittivity. If presented in terms of conductivity, the novel features are lost. This warns against insisting that a log-log plot of conductivity vs. frequency is optimal to reveal and interpret the dynamics of ionic conductors.

Effects of steroid with repetitive procaine HCl injection in the management of carpal tunnel syndrome: An ultrasonographic study

Background and aimWith the use of musculoskeletal ultrasonography (MSUS), morphological changes in the median nerve have been recently reported in patients with carpal tunnel syndrome (CTS). On the other hand, the literature still lacks the information whether those changes are further altered with steroid and local anesthetic injection which is a widely used treatment in this group of patients. Therefore, the aim of our study was to explore in-vivo the effects of steroid with repetitive procaine HCl injection on the median nerve of patients with CTS. Materials and methodThis prospective clinical trial followed-up patients for 2months. 22 patients (37 median nerves) with clinical and electrophysiological evidence of CTS were included in the study. All patients received both 40mg of triamcinolone acetonide once and 4ml of 1% procaine HCl twice a week for 2weeks with the same technique. Clinical, functional, electrophysiological and ultrasonographic evaluations were performed at the study onset, and 2months after the last injection. ResultsElectrophysiological, ultrasonographic findings (median nerve anterior–posterior diameter, transverse diameter and cross sectional area in the proximal carpal tunnel and volar bulging,) VAS scores, Boston carpal tunnel symptom and function assessment scale improved significantly (P<0.05). ConclusionSteroid injection with repetitive procaine HCl injection effectively reduced the symptoms of CTS, improved the Boston carpal tunnel symptom and function assessment scale and also electrophysiological and ultrasonographic findings. Long term effects remain to be studied. Indisputably, the use of MSUS seems to be promising in this regard.

Triamcinolone acetonide vs procaine hydrochloride injection in the management of carpal tunnel syndrome: Randomized placebo-controlled study

The aim of this trial was to compare the efficacy of triamcinolone acetonide and procaine HCl with that of placebo in the treatment of carpal tunnel syndrome. This prospective, randomized placebo-controlled trial included 57 patients (90 median nerves). Ninety median nerves were randomly assigned to 1 of 3 groups: group 1 was injected with 1 ml 0.09% saline, group 2 was injected with 40 mg triamcinolone acetonide, and group 3 was injected with 4 ml 1% procaine HCl. Clinical and electrophysiological evaluations were performed at study onset, and at 2 and 6 months post-treatment. At study onset no significant differences were observed between groups with respect to clinical and electrophysiological parameters. Clinical and electrophysiological evaluations was improved significantly in groups 2 and 3 at post-treatment (p<0.05). No significant changes were observed in group 1 (p>0.05). Moreover, groups 2 and 3 had better scores than group 1 at 2 and 6 months post-treatment(p<0.05). There was no difference between groups 2 and 3 in terms of change scores of any terms at post-treatment (p>0.05). Triamcinolone acetonide and procaine HCl injections are effective regarding short- and long-term outcomes compared with placebo injections, and procaine HCl injection was as effective as steroid injection.

De Marco Formula effectiveness as an adjunctive therapy to prevent infected ischemic diabetic foot amputation and reduce plasma fibrinogen

Background De Marco Formula (DMF) is a new procaine chemical combination of Procaine HCl and polyvinylpyrrolidone. A prospective randomized controlled clinical trial demonstrated that infected ischemic diabetic foot treatment with DMF for 52 days as an adjuvant with conventional therapy reduced major amputations. Objective To evaluate the possible association of clinical effectiveness and plasma fibrinogen reduction with DMF therapy. Methods Adult patients, 24 male/23 female, suffering from infected ischemic diabetic foot ulcers were randomly assigned to receive conventional therapy alone (group A, N = 24) or combined with DMF (receiving 0, 15 ml/kg day i.m.) for ten days and then twice a week until lesion healing or completion of 52 days (group B, N = 23). Fibrinogen concentrations were determined before and after a ten-day treatment period. Treatment clinical responses were considered favorable if major amputations were not needed. Pre and post-treatment fibrinogen values were compared within each group and between groups. Differences were considered statistically significant for p < 0, 05. Results Fifty percent of group A patients (12/24) and 21.7% of the Group B (5/23) showed unfavorable responses (a 56.6% reduction for group B). There were not statistical differences between pre and post-treatment fibrinogen within Group A (406.7 ± 49.08 vs. 354.6 ± 62.5, p = 0,11). However, post-treatment values were significantly lower within Group B (298.9 ± 15.24 vs. 487.1 ± 49.08, p = 0, 0016). Patients who showed favorable responses had statistically lower fibrinogen concentrations than those with unfavorable responses (280 ± 5.1 vs. 310 ± 7,1, p = 0.002) within group B. Conclusion DMF combined with conventional therapy for infected ischemic diabetic foot was associated with plasma fibrinogen decrease.

Thermodynamic Study of the Solubility of Procaine HCl in Some Ethanol + Water Cosolvent Mixtures

By using the van’t Hoff and Gibbs equations, the thermodynamic functions of Gibbs energy, enthalpy, and entropy of solution for procaine HCl in ethanol + water cosolvent mixtures were evaluated from solubility data determined at temperatures from (278.15 to 308.15) K. The drug solubility was greatest in neat water and lowest in neat ethanol at all of the temperatures studied. This behavior showed the negative cosolvent effect for this electrolyte drug in this solvent system. By means of enthalpy−entropy compensation analysis, a nonlinear ΔHsoln0-app versus ΔGsoln0-app plot with a positive slope from neat ethanol up to 0.10 mass fraction of water and negative from 0.10 to 0.30 mass fraction of water was obtained, whereas from this composition up to neat water a positive slope was obtained again. Accordingly to this result and to the transfer properties, it follows that the dissolution process of this drug in ethanol-rich and water-rich mixtures is enthalpy-driven, whereas between 0.10 and 0.30 mass fractio...

Characterisation and controlled drug release from novel drug-loaded hydrogels

Hydrogel based devices belong to the group of swelling controlled drug delivery systems. Temperature responsive poly( N-isopropylacrylamide)–poly(vinylpyrrolidinone) random copolymers were produced by free radical polymerisation, using 1-hydroxycyclohexylphenyketone as an ultraviolet-light sensitive initiator, and poly(ethylene glycol) dimethacrylate as the crosslinking agent (where appropriate). The hydrogels were synthesised to have lower critical solution temperatures (LCST) near body temperature, which is favourable particularly for ‘smart’ drug delivery applications. Two model drugs (diclofenac sodium and procaine HCl) were entrapped within these xerogels, by incorporating the active agents prior to photopolymerisation. The properties of the placebo samples were contrasted with the drug-loaded copolymers at low levels of drug integration. Modulated differential scanning calorimetry (MDSC), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and atomic force microscopy (AFM) were used to investigate the influence of the drugs incorporated on the solid-state properties of the xerogels. MDSC and swelling studies were carried out to ascertain their effects on the LCST and swelling behaviour of the hydrated samples. In all cases, drug dissolution analysis showed that the active agent was released at a slower rate at temperatures above the phase transition temperature. Finally, preliminary in vitro cytotoxicity evaluations were performed to establish the toxicological pattern of the gels.

Apparent Molal Volumes of Lidocaine−HCl and Procaine−HCl in Aqueous Solution as a Function of Temperature

Apparent molal volumes of two local anesthetics, lidocaine HCl and procaine HCl, in water at (298.15, 303.15, and 310.15) K have been measured in the concentration range from (0.01 to 0.1) mol·kg-1. The densities were obtained with a magnetic float densimeter. The concentration dependence of Vφ has been calculated using the Redlich and Meyer equation. The values of apparent molal volumes at infinite dilution, , the empirical constants BV, and the partial molal expansibilities, , were calculated. The results are interpreted in terms of competitive effects between electrostriction and hydrophobic solvation.

Colorimetric determination of benzocaine, lignocaine and procaine hydrochlorides in pure form and in pharmaceutical formulations using p-benzoquinone.

A simple, accurate and sensitive method for the microdetermination of benzocaine, lignocaine and procaine hydrochlorides in pure forms and in pharmaceutical formulations is described. The procedure is based on the reaction of those drugs in an aqueous acidic medium with p-benzoquinone to form charge-transfer complexes. The method has been used for the determination of 5.0-70, 5.0-60 and 5.0-90 microg ml(-1) of benzocaine, lignocaine HCl and procaine HCl, respectively. The complexes have apparent molar absorptivities of 1.70 x 10(3), 2.79 x 10(3) and 2.42 x 10(3) L mol(-1) cm(-1) and Sandell sensitivities of 9.72, 10.34 and 11.25 ng cm(-2), respectively. The proposed procedure of analysis is as accurate as the British Pharmacopoeial method (2003). The method was successfully used for the determination of those drugs in the presence of their degradation products, additives and excipients, which were normally encountered in pharmaceutical formulations.

Complex formation between the anionic polymer (PAA) and a cationic drug (procaine HCI): characterization by microcalorimetric studies.

Due to the importance of drug-polymer interactions in, inter alia, drug loading/release, supramolecular assemblies and DNA delivery for gene therapy, the aim of this study was therefore to establish the mechanism of interaction between a model polymer (Polyacrylic acid, PAA) and a model drug (procaine HCl). This was performed by studying the effect of salt (KCl) concentration on their heat released values using Isothermal Titration Microcalorimetry (ITM). The integrated released heat data were computer fitted to a one class binding model and the thermodynamic parameters (Kobs, deltaH, and N) were determined. As the KCl concentration was increased, Kobs decreased thus establishing the salt dependence of the interaction. The linear variation of deltaGobs with deltaSobs indicated that their interaction was entropically driven. The stoichiometry of the interaction was calculated to be one procaine molecule per monomer of PAA. Dissection of the total observed free energy at each KCI concentration indicated that the contribution of the non-electrostatic attractions to the interaction of PAA with procaine HCl was greater than those of the electrostatic attractions. We have shown that the interaction between PAA and procaine HCl is dependent upon the presence of counterions (monovalent ions) and is mainly entropically driven. The calculated stoichiometry indicated that one procaine HCl molecule neutralised one carboxylic acid group on PAA. Although electrostatic interactions were necessary for initiating complex formation, the non-electrostatic forces were dominant in stabilising the PAA-procaine HCl complex.

Effects of local anesthetics on rat leukocyte functions

To determine whether local anesthetics affect functions in macrophages, I examined the effects of 5 local anesthetics, lidocaine HCl, mepivacaine HCl, propitocaine HCl, procaine HCl, and tetracaine HCl, on chemotaxis and production of superoxide anion in rat peripheral macrophages. Rats were intraperitoneally injected with 1% glycogen. Peritoneal exudate cells containing macrophages were obtained from the peritoneal cavity 4 days after the administration. Chemotaxis was evaluated using a 48-well microchemotaxis chamber with a polycarbonate membrane filter. Production of superoxide anion was measured spectrophotometrically by a superoxide dismutase-sensitive reduction of ferricytochrome c. All of the local anesthetics examined at a dose of 1 mg ml inhibited (P < 0.05) chemotaxis and production of superoxide anion in macrophages. Moreover, pretreatment of macrophage suspensions with mepivacaine HCl, propitocaine HCl, procaine HCl, or tetracaine HCl at a dose of 1 mg ml resulted in inhibition of the production of superoxide anion. In contrast, pretreatment with lidocaine HCl at this concentration did not significantly affect the production of superoxide anion. These results suggest that all of the local anesthetics examined at a therapeutic concentration inhibit chemotaxis and production of superoxide anion in rat macrophages.

Simultaneous High-Performance Liquid Chromatographic Analysis for Famotidine, Ranitidine HCl, Cimetidine, and Nizatidine in Commercial Products

A high-performance liquid chromatographic (HPLC) procedure for the simultaneous determination of famotidine (FMT), ranitidine HCl (RNT), cimetidine (CMT), and nizatidine (NZT) was developed using a two-level, full-factorial design with three variables (volume of methanol, percentage of triethylamine, and concentration of phosphate buffer) to select an acceptable mobile phase. A column (15cm × 4.6 mm ID) of Inertsil ODS-2 (5 μm) was used, and 0.04M aqueous sodium dihydrogen phosphate/acetonitrile/methanol/TEA at a proportion of 345/20/35/0.7 (v/v/v/v) was the selected mobile phase (1 ml/min). The detection wavelength was set at 230 nm, and procaine HCl was used as the internal standard. Precision and linearity of the method were assessed. None of the commercial samples was found to be outside the compendial limits of 90.0% to 110.0% of the claim amount.