RESUMEN

Calcium carbonate is a chemical compound with the formula CaCO3 formed by three main elements: carbon, oxygen, and calcium. It is a common substance found in rocks in all parts of the world (most notably as limestone), and is the main component of shells of marine organisms, snails, coal balls, pearls, and eggshells. CaCO3 exists in different polymorphs, each with specific stability that depends on a diversity of variables.

Asunto(s)

RESUMEN

A complex of low molecular weight chitosan (LMWC) with oleic acid and diclofenac potassium (DP) was prepared and dispersed in high concentrations of polysorbate 20, 60 and 80 in water to form a solution which releases its components slowly. The formed complex was characterized using different analytical methods. The size of the resulted nanoparticles and the effect of tweens on size were followed using dynamic light scattering (DLS). The release of DP from this delivery system was monitored by altering the molecular weight of chitosan and the type and concentration of the polysorbates used. The most suitable preparation consisted of DP, LMWC 13 kDa, and oleic acid. This was dispersed in 5% Tween 80 and the release was followed by the adaptation of USP II apparatus using a cellophane bag. This preparation offers a release of up to 24 h.

Asunto(s)

RESUMEN

We present herein a new herbal combination called Etana that is composed of five herbal extracts including Panax quinquelotius (Ginseng), Eurycoma longifolia (Tongkat Ali), Epimedium grandiflorum (Horny goat weed), Centella asiatica (Gotu Kola) and flower pollen extracts. Most of the above-mentioned extracts have a long historical and traditional use for erectile dysfunction (ED). On the basis of the mechanism of action of each of the above, a combination is introduced to overcome several physiological or induced factors of ED. This study was conducted to show an enhancement of erectile function in male rats. The animals were observed for 3 h after each administration for penile erection, genital grooming and copulation mounting, and the penile erection index (PEI) was calculated. The maximum response was observed at the concentration of 7.5 mg kg(-1) of Etana. At a 7.5 mg kg(-1) single dose, the percentage of responding rats was 53+/-7 with a PEI of 337+/-72 compared with 17+/-6 with a PEI of 30+/-10 for control animals. This PEI was significantly (P<0.001) higher than each single component and than the sum of any two herbal components of Etana. When compared with sildenafil citrate, Etana induced more pronounced PEI than 0.36 mg kg(-1), but similar to 0.71 mg kg(-1) of sildenafil. Furthermore, full acute and sub-acute toxicity studies showed no toxic effects of Etana. In conclusion, this study describes a new and safe combination of herbal components that enhance erectile function in male rats. Clinical studies are warranted for evaluating Etana's significance in ED.

Asunto(s)

RESUMEN

Spectroscopic and phase solubility techniques have been used to study the complexation of neutral meloxicam (Mel) with alpha-, beta-, gamma- and HP-beta-cyclodextrins (CDs). The results indicate that neutral Mel has two conformational structures, enol and zwitterions, with the latter more dominant in water. The two pK(a)s of Mel were found to change in the presence of beta-CD, where a blue shift in lambdamax was observed but not in the presence of alpha, HP-beta- and gamma-CD. Rigorous analysis of phase solubility diagrams indicate that beta- and HP-beta-CD form 1:2 Mel/beta-CD type complexes with Mel while alpha- and gamma-CD form only 1:1 complexes. The fact that the overall 1:2 Mel/CD complex formation constant (beta12) was found significantly higher for beta-CD than for HP-beta-CD, combined with further spectroscopic studies, indicate that beta-CD favors inclusion of the neutral enol form over the zwitterion. Unlike alpha-, HP-beta- and gamma-CDs, the hydrophobic microenvironment of a tight 1:2 Mel/beta-CD complex was found to mimic those of organic solvents, thus favoring inclusion of the enol rather than the zwitterion, and hence shifting the tautomerization equilibrium towards the enol conformer.

Asunto(s)

RESUMEN

An HPLC method was developed and validated for the determination of cetirizine dihydrochloride (CZ) as well as its related impurities in commercial oral solution and tablet formulations. Furthermore, two preservatives associated with the drug formulations, namely, propyl (PP) and butylparabens (BP) were successfully determined by this method. The chromatographic system used was equipped with a Hypersil BDS C18, 5 microm column (4.6 x 250 mm) and a detector set at 230 nm in conjunction with a mobile phase of 0.05 M dihydrogen phosphate:acetonitrile:methanol:tetrahydrofuran (12:5:2:1, v/v/v/v) at a pH of 5.5 and a flow rate of 1 ml min(-1). The calibration curves were linear within the target concentration ranges studied, namely, 2 x 10(2) - 8 x 10(2) microg ml(-1) and 1-4 microg ml(-1) for CZ, 20-100 microg ml(-1) for preservatives and 1-4 microg ml(-1) for CZ related impurities. The limits of detection (LOD) and quantitation (LOQ) for CZ were, respectively, 0.10 and 0.34 microg ml(-1) and for CZ related impurities were in the ranges of 0.08-0.26 microg ml(-1) and 0.28-0.86 microg ml(-1), respectively. The method proved to be specific, stability indicating, accurate, precise, robust and could be used as an alternative to the European pharmacopoeial method set for CZ and its related impurities.

Asunto(s)

RESUMEN

This article studies the compatibility of amlodipine besylate in its solid formulations with various drug excipients. The various factors affecting amlodipine besylate stability were studied using high-performance liquid chromatography (HPLC). It has been found that binary 1:1 mixtures of amlodipine besylate and an excipient are stable at 65 degrees C and 40 degrees C/75% RH. Further investigations were conducted to study the stability of amlodipine besylate in multicomponent mixtures, including mixtures with actual formulations. The study reveals that mixtures of lactose, magnesium stearate, and water induce some instability on amlodipine besylate. The major degradation product confirmed by HPLC-mass spectrometry is amlodipine besylate glycosyl. This is in conformity with the well-known Maillard reaction between primary amines and lactose. Thus, lactose-free amlodipine formulations are recommended from the safety, quality, efficacy, and process cost points of view.

Asunto(s)

RESUMEN

JPM8 is a novel sildenafil-like PDE5 inhibitor. Its efficacy was tested in vivo by the oral administration of drugs to a rat model and recording penile activity changes. Effect on the relaxation of the rabbit cavernosa was tested in vitro using an organ bath were drugs are added to the tissue media and relaxation was recorded using a transducer connected to a chart recorder. The accumulation of cGMP and cAMP was measured by incubation of cavernosa strips and then extracting the produced cGMP and cAMP in the incubation mixture, then quantitating it using ELISA. JPM8 showed increased and promoted sexual and penile activity in rats in a similar but slightly higher trend than the positive control sildenafil. JPM8 was more efficient in relaxing the rabbit corpora cavernosa than sildenafil. The cGMP and cAMP accumulation showed a similar trend for both drugs. We concluded that JPM8 was very effective in promoting sexual activity in rats, relaxing the corpora cavernosa and promoting cGMP accumulation in rabbits.

Asunto(s)

RESUMEN

There is a lack of information concerning analysis of terbutaline sulfate and quantification of its related substances particularly in the liquid dosage forms. This work aimed at developing and validating an HPLC method for determination of terbutaline sulfate and its possible degradation products, namely, 3,5-dihydroxybenzoic acid, 3,5 dihydroxybenzaldehyde and 1-(3,5-dihydroxyphenyl)-2-[(1,1-dimethylethyl) amino]-ethanone that might appear as impurities in the starting material as well as in the solid and liquid formulations. The chromatographic system used consisted a Hypersil 100 C(18,) 150 x 4.6 mm (5 microm) column, a mobile phase of ammonium acetate (0.15 M) and glacial acetic acid (pH of 4.0, 96:4 v/v) with a flow rate of 2 ml min(-1) and a UV detector set at 270 nm. The degree of linearity and the characteristic statistical parameters of the calibration curves including the limit of detection (LOD) and limit of quantitation (LOQ) were estimated for terbutaline sulfate and its degradation products. The method was found to be specific, stability indicating, accurate, precise and robust.

Asunto(s)

RESUMEN

Ferula harmonis, which is locally called 'zallouh' in the Middle East, is used as an aphrodisiac as it is reputed to enhance male sexual behavior, however, there is no scientific verification. In this study, the oil extracted from the seeds of Ferula harmonis was tested for its efficacy in enhancing erectile function and toxicity in male rats. The sexual activities assessed by penile erection index were dose dependent. The ED(50) (12.03 mg/kg) was 880 times less than the LD(50) (10.6 g/kg). However, when doses ranging from 0.05, 0.5 to 2 g/kg were given daily for 28 days, acute and subacute toxicity were observed. There was a decrease in total body weight, hepatomegaly, atrophic testis, significant decrease in hemoglobin and red blood cell count. In addition, there was a significant decrease in cholesterol level. All the above indicate that the crude oil from the plant Ferula harmonis can enhance erectile function, however, it becomes toxic if it is used for a long period of time. Further studies are underway to isolate and identify the active ingredients and their exact mechanisms of action.

Asunto(s)

RESUMEN

This study aimed at developing and validating an HPLC method for the assay of sildenafil citrate and its related substances that might coexist in the drug commercial products and in tablets' formulation as impurities that originate from synthesis processes or degradation. A chromatographic system comprising a microBondapak C(18) (10 microm) column, a mobile phase of ammonium acetate (pH 7.0, 0.2 M)-acetonitrile (1:1, v/v), a flow rate of 1 ml/min and a UV detector set at 240 nm has shown good chromatographic separation for sildenfil and the other related substances. The degree of linearity of the calibration curves, the percent recoveries of sildenafil and related substances, the limit of detection, LOD, and limit of quantitation, LOQ for the HPLC method have been determined. The HPLC method under study was found to be specific, precise, accurate, reproducible indicating stability and robust.

Asunto(s)

RESUMEN

The chemical stability of enalapril maleate in tablet dosage forms consisting of different formulation excipients has been studied in this work. The influence of various parameters such as heat, moisture, light and the drug-matrix was investigated. The degradation of enalapril maleate has been followed by using an HPLC method, which was demonstrated to be specific, stability indicating, accurate and precise. The degradation kinetics of enalalpril maleate in phosphate buffer solutions of pH values in the range of 2.2-10.5 were observed to be psuedo first order throughout the whole pH range studied. Enalapril maleate alone showed high stability for temperature under dry and humid conditions, however it became unstable when mixed with the drug-matrix in its tablet formulations and exposed to the same conditions. The pathway of degradation of enalapril maleate was found to be pH dependent. The extent of degradation of two different enalapril maleate tablet formulations (product A of a basic drug-matrix and product B of an acidic drug-matrix) has been investigated. The degree of degradation of the product with acidic matrix was significantly less than that of the basic matrix under same temperature and humidity conditions. In fact, diketopiperazine and enalaprilat degradants were mainly associated with the degradation of the product with the acidic matrix and that with the basic matrix, respectively. Dry enalapril maleate powder showed some photolysis, which was more significant with daylight (3.3%) compared with that under UV light (0.2%). Although the product with the acidic matrix showed some photolysis but the effect was not pronounced and the % recovery of enalapril was almost complete and within the acceptable experimental errors. However, the product with the basic matrix showed almost no response for photolysis.

Asunto(s)

RESUMEN

Parameters affecting the characteristics of the drug loaded crosslinked sodium alginate matrix films and the release of metoclopramide hydrochloride and cisapride from these matrices were studied. It was shown that the release rate is influenced by the crosslinking technique of the matrix film, crosslinker type and concentration, drug physico-chemical properties especially solubility and the molecular weight, acidity of the release medium, concentration and the loaded quantity of the drug in the matrix. The crosslinking process of the matrix film was shown to be an interfacial phenomenon and the nature of crosslinking depends on the crosslinker type and concentration. This work also showed that crosslinked alginate in a matrix form has limitation in practical use due to the effect of acidic medium on the crosslinking of the matrix film and hence, the rate of drug release.

Asunto(s)

RESUMEN

The aim of this study was to develop models for rigorous analysis of phase solubility diagrams, particularly the descending portion, in order to obtain individual thermodynamic complex formation and solubility product constants. Additionally, the effect of varying the initial solute concentration St, in excess of the optimal solubility Sm, on the general shape of the plateau and descending portions of the solubility diagram was investigated. The solubilities of propylpapraben (Seq) were measured against initial beta-cyclodextrin concentrations (Lt) at different temperatures and different St. Equilibrium concentrations (Leq) were also measured. The only effect observed was a broadening of the plateau region with increase in St with no discernible effect on Sm. Simultaneous rigorous analysis of the rising as well as the descending portions of the phase diagram could only be interpreted in terms of formation of two soluble complexes: SL and S2L. Rigorous analysis of the descending portion allowed the determination of individual formation constants K11 (SL) and K21 (S2L) in addition to the solubility product of the less soluble complex KS11 (SL). Thermodynamic analysis of the individual solubility of propylparaben and beta-cyclodextrin was carried out in water at different temperatures. In aqueous beta-cyclodextrin solutions, however, the solubility of propylparaben is enhanced due to the formation of both SL (delta G11(0) = -26.4 kJ/mol) and S2L (delta G21(0) = -46.4 kJ/mol) soluble complexes. Formation of the SL-complex is favored both by enthalpy (delta H11(0) = -20.7 kJ/mol) and a slight increase in entropy (delta S11(0) = 18.6 J/mol.K). Formation of S2L from SL apparently involves stronger solute-SL binding (delta H21(0) = -45.9 kJ/mol) yet is retarded by a net decrease in entropy (delta S21(0) = -86.3 J/mol.K). The solubility of the SL-complex is highly endothermic (delta HS11(0) = 55.8 kJ/mol), and although is accompanied by much randomization (delta SS11(0) = 101.8 J/mol.K), its solubility remains quite low (delta GS11(0) = 25.5 kJ/mol). Molecular mechanical modeling of propylparaben/beta-cyclodextrin interactions in water revealed that the S2L-complex formation is energetically more favored.

Asunto(s)

RESUMEN

The bioavailability of two pharmaceutical dosage forms formulated using different polymorphs of tenoxicam were compared. Serum levels of TNX were analysed using high performance liquid chromatography. The pharmacokinetic parameters were estimated following the oral administration of a single dose (20 mg) of the drug as two different polymorphs to 12 healthy volunteers. The differences between formulations were statistically insignificant.

Asunto(s)

RESUMEN

The paper describes a comparative bioavailability study on two tablet formulations containing 100 mg of tetroxoprim and 250 mg of sulphadiazine. The comparison was based on the estimated pharmacokinetic parameters from time--serum concentration profiles obtained following the administration of the tablets to 12 healthy volunteers. Statistical analysis performed on the parameters showed that the differences are statistically insignificant and the formulations are bioequivalent.

Asunto(s)

RESUMEN

Quantitative determination of tetroxoprim and sulphadiazine in serum and urine was performed using reversed phase high performance liquid chromatography. Protein precipitation using 10% perchloric acid was utilized for purification of serum samples while urine samples were diluted prior to analysis. The mobile phase consisted of triethylammonium acetate buffer (85%), acetonitrile (12%) and methanol (3%), with a final pH of 4.2. The eluent was monitored at 280 nm. Benzoic acid was used as an internal standard. Standardization, validation and application of the method is described.

Asunto(s)

RESUMEN

The bioavailability of two brands of ranitidine tablets was studied in 10 healthy volunteers. Formulation factors were compared by performing disintegration, dissolution and content uniformity tests. Plasma concentrations of ranitidine were measured using a sensitive and precise high pressure liquid chromatographic (HPLC) procedure. Pharmacokinetic parameters were determined for both formulations and included: Cmax, AUCt, AUC infinity, tmax, t1/2 and the terminal rate of elimination (k). Statistical analysis revealed that differences between the brands were not significant. The two formulations can be considered to be bioequivalent.

Asunto(s)

RESUMEN

Synopsis The preparation and characterisation of purified C(10) to C(18) even-numbered triethano-lamine alkyl sulphates are described. Critical micelle concentrations were determined at 25 degrees C, using both conductance and drop volume methods. The authenticity and purity of the products are established, and evidence presented for amending the accepted melting points for two of the compounds.

RESUMEN

Synopsis The foaming properties of solutions of purified samples of the C(10) to C(18) even-numbered sodium alkyl sulphates in water have been studied using three methods of foam generation. Foam volumes increased with increase in surfactant concentration, and reached a limiting value at the C.M.C. At post-C.M.C. concentrations, foam volumes increased to a maximum with temperature, and then decreased. The point at which the maximum occurred, the maximum foam temperature (M.F.T.), varied from one surfactant to another, but was independent of the experimental method. M.F.T. was inversely proportional to the hydrophile-lipophile balance (H.L.B.) value. The corresponding triethanolamine salts behaved in the same way. Similar results were observed with non-ionics, but the plots of H.L.B. value against M.F.T. were positive.