Isoxsuprine Hydrochloride Research Articles

Fabrication of biosensor based on Chitosan-ZnO/Polypyrrole nanocomposite modified carbon paste electrode for electroanalytical application

A sensitive conductive nanocomposite sensor consisting of chitosan, zinc oxide nanoparticles, and polypyrrole was developed. The sensor was prepared by oxidative polymerization of pyrrole using (NH4)2S2O8 as the oxidant followed by mixing a Chitosan-Zinc oxide composite with a different content of Chitosan. The morphology and surface area of the nanocomposites were changed by changing the percentage of chitosan. The newly developed nanocomposites also showed a significant improvement in electrical conductivity as mentioned from the cyclic voltammetry measurements of the K3[Fe(CN)6] sample. A square-wave adsorptive anodic stripping voltammetry method successfully measured Isoxsuprine hydrochloride using different types of nanocomposite modified CPEs and showed a large enhancement of stripping peak current compared to bare CPE. Consequently, the proposed sensors proved to have a promissing feature for applications in biosensors.

Exploring isoxsuprine hydrochloride binding with human serum albumin in the presence of folic acid and ascorbic acid using multispectroscopic and molecular modeling methods

Isoxsuprine hydrochloride (vasodilator drug), folic acid and ascorbic acid are medicines which can be utilized alone or simultaneously by pregnant women. In the present work the competitive binding of isoxsuprine hydrochloride (ISO) with human serum albumin (HSA) in the absence and presence of folic acid (FOL) and ascorbic acid (AS) was investigated using different spectroscopic probes and molecular docking studies. The results of fluorescence suggested that isoxsuprine alone or in the presence of ascorbic acid can bind to HSA and quench the fluorescence of HSA with static mechanism but For HSA–folic acid–isoxsuprine system, dynamic type of quenching mechanisms is involved. The values of binding constants (KHSA–ISO~1.2×103M−1, KHSA–AS–ISO~2.1×103M−1and KHSA–FOL–ISO~0.7×103M−1) suggested that affinity of HSA to isoxsuprine increased in the presence of ascorbic acid while the presence of folic acid reduced the affinity of protein to isoxsuprine. The results of FT-IR and circular dichroism measurements indicated that the binding of isoxsuprine to HSA in the absence and the presence of folic acid and ascorbic acid may induce conformational and microenvironmental changes of protein. Not only do these types of spectroscopy techniques provide all the information about the systems, molecular docking, also emphasizes the results and is employed for the identification of the active site residues, bioactive conformer of Isoxsuprine and their critical interactions.

Spectrofluorimetric determination of certain adrenergic agonist drugs in their pure forms and pharmaceutical formulations: Content uniformity test application.

A new, simple, sensitive and rapid spectrofluorimetric method has been developed for determination of certain adrenergic agonists such as isoxsuprine hydrochloride, ritodrine hydrochloride and etilefrine hydrochloride in their pure forms and pharmaceutical dosage forms. The method depends on micellar enhancement of the native fluorescence of investigated drugs by using 2% w/v sodium dodecyl sulfate (SDS) as an anionic surfactant. The enhanced fluorescence intensity of investigated drugs was measured at 305nm after excitation at 278nm. The interaction of studied drugs with SDS was studied, and the enhanced fluorescence intensity was exploited to develop an assay method for the determination of investigated drugs. The relative fluorescence intensity-concentration plots were rectilinear over the range 0.15-3.00μgml-1 , with low quantification limits of 0.132, 0.123 and 0.118μgmL-1 for isoxsuprine, ritodrine and etilefrine, respectively. The proposed method was successfully applied for determination of studied drugs in their pharmaceutical formulations. Moreover, the high sensitivity of the proposed method allows performing the content uniformity testing of the studied drugs in their tablets by using the official United States Pharmacopeia (USP) guidelines. Statistical comparisons of the results with those of the reported methods revealed excellent agreement and indicated no significant difference in accuracy and precision.

Blend microspheres of chitosan and polyurethane for controlled release of water-soluble antihypertensitive drugs

Blend microspheres of chitosan and polyurethane (PU) have been prepared by water-in-oil emulsion cross-linking method and used to encapsulate two water-soluble and having widely different plasma half-life cardiovascular drugs, viz., isoxsuprine hydrochloride and calcium dobesilate. The blend miscibility of the polymers was confirmed by differential scanning calorimetry at >60 wt% of PU. The microspheres were characterized by scanning electron microscopy to understand the morphology of the drug-loaded microspheres. Chemical interactions between drug molecules and the carrier polymers have been investigated by Fourier transform spectroscopy. XRD measurements on placebo matrices, drug-loaded formulations and nascent drugs indicated their uniform dispersion in the polymer matrix. In vitro release experiments performed in both acidic pH of 1.2 and alkaline pH of 7.4 increased the release time of both the drugs in the media employed. Kinetics of drug release was analyzed by empirical equation, suggesting the deviation from Fickian transport to non-Fickian trend.

Identification of isoxsuprine hydrochloride as a neuroprotectant in ischemic stroke through cell-based high-throughput screening.

Stroke is a leading cause of death and disability and treatment options are limited. A promising approach to accelerate the development of new therapeutics is the use of high-throughput screening of chemical libraries. Using a cell-based high-throughput oxygen-glucose deprivation (OGD) model, we evaluated 1,200 small molecules for repurposed application in stroke therapy. Isoxsuprine hydrochloride was identified as a potent neuroprotective compound in primary neurons exposed to OGD. Isoxsuprine, a β2-adrenergic agonist and NR2B subtype-selective N-methyl-D-aspartate (NMDA) receptor antagonist, demonstrated no loss of efficacy when administered up to an hour after reoxygenation in an in vitro stroke model. In an animal model of transient focal ischemia, isoxsuprine significantly reduced infarct volume compared to vehicle (137±18 mm3 versus 279±25 mm3, p<0.001). Isoxsuprine, a peripheral vasodilator, was FDA approved for the treatment of cerebrovascular insufficiency and peripheral vascular disease. Our demonstration of the significant and novel neuroprotective action of isoxsuprine hydrochloride in an in vivo stroke model and its history of human use suggest that isoxsuprine may be an ideal candidate for further investigation as a potential stroke therapeutic.

Non-aqueous and two-phase titrimetric assay of isoxsuprine hydrochloride in pharmaceuticals

Based on the nitrogenous base or quaternary ammonium moiety in isoxsuprine hydrochloride (ISX), two highly accurate and selective titrimetric methods are proposed f or the determination of ISX in spiked human urine, injection and tablets. Non-aqueous titration (Method A) involves removal of protonated amine using mercuric acetate for enhanced basic nitrogen prior to titration with perchloric acid in an acetic acid medium using crystal violet as indicator. Two-phase titration (Method B) is based on ion association complex formation between sodium lauryl sulphate (SLS) and protonated amine of ISX at pH 2.5 in aqueous phase, end point being detected by change in dimethyl yellow color in chloroform layer. The methods are applicable over the concentration range 2.0–20.0 mg and 1.0–10.0 mg for method A and method B, respectively. Calculations are based on 1: 1 molar ratio, i.e., JSX: HClO4 for method A and ISX: SLS for method B, owing to the presence of one nitrogen atom. Method A is applicable to the determination of ISX in tablets whereas method B is applicable to spiked human urine, injection and tablets. The methods are validated statistically by comparing the results with those of the reference method by applying the Student’s t-test and F-test. The accuracy was further ascertained by recovery studies via standard addition technique.

Spectrophotometric Methods for the Estimation of Isoxsuprine Hydrochloride in Bulk and Oral Dosage Form

Four new, simple, sensitive and reproducible spectrophotometric methods have been developed for the estimation of isoxsuprine hydrochloride in tablet dosage form. Method A involves the determination of isoxsuprine hydrochloride by Q-absorbance ratio method at 269nm and 274nm; the Beer's concentration range was found to be 20-100 µg/mL. Method B and Method C involves the determination of isoxsuprine hydrochloride by first derivative spectrophotometry and second derivative spectrophotometry respectively. The normal spectrum was derivatized to first and second order derivative spectrum and the linearity was found to lie within the Beer's range for isoxsuprine hydrochloride. Method D involves the determination of isoxsuprine hydrochloride by Area under curve method (AUC) and the linearity was established. The correlation coefficient for all the four methods were found to be 0.999 and the developed methods were analyzed for specificity, limit of detection (LOD), limit of quantification (LOQ), linearity of response, precision and accuracy. Thus the proposed methods could be adopted for routine analysis of bulk drug and its formulation. Keywords: Area under curve (AUC), Beer's law, Derivative Spectrophotometry, Isoxsuprine hydrochloride, Q-Absorbance ratio

Pharmacokinetics of Isoxsuprine Hydrochloride Administered Orally and Intramuscularly to Female Healthy Volunteers

Isoxsuprine (1-(4-hydroxyphenyl)-2-(1-methyl-2-phenoxyethylamino)-1-propanol, CAS 395-28-8) is a peripheral vasodilator that also stimulates beta-adrenergic receptors. It causes a direct relaxation of vascular and uterine smooth muscles and produces positive inotropic and chronotropic effects. It is widely used to arrest premature labour and miscarriage. The aim of this trial was to investigate the pharmacokinetics of isoxsuprine hydrochloride administered orally to healthy young female volunteers as an extended-release formulation at the doses of 30, 60 and 90 mg compared to 10 mg by i.m. route. A randomised, crossover, four-period, multisequence, single-dose design was adopted. Plasma and urine concentrations of free and total isoxsuprine were evaluated by tandem mass spectrometry that reached a low quantification limit of 1 ng/ml. From plasma concentrations Cmax, tmax, AUC(0-t), AUC(0-infinity), t1/2 and Vd and from urine concentration CUE(0-24h) were evaluated by the non-compartmental model. The free drug was present only in plasma after i.m. route, whereas total isoxsuprine, namely the drug after an enzymatic hydrolysis of the conjugate form, was detected in all plasma and urine samples. The distribution volume of the free drug proved to be 2.5 times higher than that of total isoxsuprine, which indicates a good penetration of the free drug into tissue compartments. Oral absorption was evaluated from the p.o./i.m. percentualized ratio of AUC and CUE and proved to be on average around 51%, being linearly correlated with the three doses administered. The oral absorption proved to be sustained as expected from the zero-order kinetics of the drug release from the core of the extended-release formulation. This has justified different values of half-life that was on average 2.2 h after the i.m. route and around 10 h after the three oral doses. After isoxsuprine administration, both oral and i.m. routes, the heart rate increased from baseline during the 9 h monitoring period. This was an expected finding attributable to the stimulating activity of beta-adrenergic receptors. The tolerability of isoxsuprine proved to be very good with all the four administrations performed.

Use of isoxsuprine hydrochloride as a tocolytic agent in the treatment of preterm labour: a systematic review of previous literature.

The aim of this systematic review was to evaluate the efficacy of isoxsuprine (1-(4-hydroxyphenyl)-2-(1-methyl-2-phe-noxyethylamino)-1-propanol, CAS 395-28-8), a tocolytic agent used in both preterm labour and risk of abortion. Two analyses were conducted on data reporting the use of isoxsuprine in the prevention of preterm delivery. The first analysis examined two double-blind studies to determine the effect of isoxsuprine compared to placebo. The second analysis reviewed data from 25 publications containing individual and general patient data. Main outcome measures included delay of pregnancy and patient outcome. Analysis of double-blind studies demonstrated a positive outcome with isoxsuprine in 92% of cases compared to placebo control (44.4%, p < 0.001). This beneficial effect was maintained when either risk of abortion (92.5% in isoxsuprine treated compared to 46.4% in placebo, p < 0.001) or risk of premature delivery (89.5% in isoxsuprine treated compared to 29.4% in placebo, p < 0.001) was examined. Secondary analysis of individual patient data also revealed a beneficial effect of isoxsuprine in prolonging pregnancy in 54.5% of women at risk of abortion and in 82.3% of women at risk of premature delivery. Combination of individual and general data revealed a beneficial effect of isoxsuprine in 77.3% of cases at risk of abortion and 89% for risk of premature delivery. These findings provide preliminary evidence in favour of the effectiveness of isoxsuprine in prolonging pregnancy in women at risk of abortion or premature delivery.

Development and validation of fixed‐time method for the determination of isoxsuprine hydrochloride in commercial dosages forms

The main aim of this work was to develop a kinetic spectrophotometric method for the quantitative analysis of isoxsuprine hydrochloride in commercial tablets. The method is based on the reaction of isoxsuprine hydrochloride (ISx) with hydroxylamine hydrochloride and ammonium cerium (IV) nitrate in sulphuric acid medium at room temperature which resulted in the formation of yellow-coloured product peaking at 380 nm. The reaction is followed spectrophotometrically by measuring the absorbance as a function of time. Fixed time method (ΔA = A₄-A₂, where A₂ and A₄ refer to absorbance measurements taken at 2 and 4 min, respectively) was adopted for constructing the calibration curve which was found to be linear over the concentration range of 30-80 µgmL⁻¹ with molar absorptivity of 5.95 × 10³ L mol⁻¹ cm⁻¹. The method has been applied successfully to the determination of isoxsuprine hydrochloride in tablets. Statistical comparison (point and interval hypothesis tests) of the results showed that there is no significant difference between the proposed method and reference method.

Use of N, N-diethyl-p-phenylenediamine sulphate for the spectrophotometric determination of some phenolic and amine drugs

Spectrophotometric methods are proposed for the determination of drugs containing a phenol group [salbutamol sulphate (SLB), ritodrine hydrochloride (RTD), isoxsuprine hydrochloride (IXP)] and drugs containing an aromatic amine group [dapsone hydrochloride (DAP), sulfamethoxazole (SFM), and sulfadiazine (SFD)] in pharmaceutical dosage forms. The methods are based on coupling of N, N-diethyl-p-phenylenediamine sulphate with the drugs in the presence of KIO4 to give a green colored product (λmax at 670 nm) and a red colored product (λmax at 550 nm), respectively. Linear relationships with good correlation coefficients (0.9986-0.9996) were found between absorbance and the corresponding concentration of drugs in the range 1-7, 2-22, 1-17, 1.5-12, 2-25, and 2-21 μg mL-1 for SLB, RTD, IXP, DAP, SFM and SFD, respectively. Variable parameters such as temperature, reaction time and concentration of the reactants have been analyzed and optimized. The RSD of intra-day and inter-day studies was in the range of 0.2-1.0 and 0.4-1.0%, respectively. No interference was observed from common pharmaceutical adjuvants. The reliability and performance of the proposed methods was validated statistically; the percentage recovery ranged from 99.5 ± 0.1 to 99.9 ± 0.3%. Limits of detection were 0.14, 0.21, 0.51, 0.44, 0.33 and 0.37 μg mL-1 for SLB, RTD, IXP, DAP, SFM, and SFD, respectively.

Spectrophotometric determination of isoxsuprine hydrochloride using 3-methyl-2-benzothiazolinone hydrazone hydrochloride in spiked human urine and pharmaceuticals

Two selective and sensitive spectrophotometric methods are proposed for the determination of isoxsuprine hydrochloride (ISX) in spiked human urine and in pharmaceuticals. The methods are based on the oxidative-coupling reaction between 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) and ISX in the presence of Ce(SO(4))(2). The novelty of the proposed reaction is the formation of two different colored chromogens at two different pHs. The resulting product at pH<1.5 is a red colored chromogen peaking at 500nm (method A) and that formed between the pH 3.85 and 4.15, is violet colored with an absorption maximum at 580nm (method B). In both the methods, absorbance of the chromogen is found to increase linearly with the concentration of ISX as is corroborated by the correlation coefficients of 0.9989 and 0.9970, and the systems obey Beer's law over the ranges of 1.4-21.0 and 1.0-15.0microgml(-1), for method A and method B, respectively. The calculated molar absorptivities are 1.08 x 10(4) and 1.78 x 10(4)lmol(-1)cm(-1) for method A and method B, respectively with corresponding Sandell sensitivity values of 0.0311 and 0.0190microgcm(-2). The reaction stoichiometry, in both the methods, was evaluated by the limiting logarithmic method and was found to be 1:1 (ISX:MBTH). The methods were successfully applied to the determination of ISX in spiked human urine and pharmaceutical formulation.

A Sensitive Spectrophotometric Determination of Ritodrine, Pentazocine, Isoxsuprine Hydrochlorides and Amoxicillin in Pure and Pharmaceutical Samples

A simple, accurate and highly sensitive spectrophotometric method for the determination of ritodrine hydrochloride (RTH), pentazocine hydrochloride (PZH), isoxsuprine hydrochloride (ISH) and amoxicillin (AMX) is described. The method is based on the oxidation of the studied drugs by a known excess of chloramine – T (CAT) in hydrochloric acid medium and subsequent determination of the unreacted oxidant by reacting it with iodide in the same acid medium liberates iodine, which subsequently react with starch to form a stable starch‐iodine complex. The reacted oxidant corresponds to the drug content. The coloured complex exhibits a maximum absorption at 590 nm. The apparent molar absorptivity values and Sandell’s sensitivity values are in the range 6.96x104 ‐ 1.43x105 L mol–1 cm–1 and 2.45‐4.30 ng cm–2, respectively. The method was successfully applied to the studied drugs in their dosage forms. The results are reproducible within ±1% and compare favorably with those of official methods of British Pharmacopoeia and the United States Pharmacopoeia.

Synthesis and evaluation of uterine relaxant activity for a novel series of substituted p-hydroxyphenylethanolamines

Novel racemic 1-(4-hydroxyphenyl)-2-[3-(substituted phenoxy)-2-hydroxy-1-propyl]aminopropan-1-ol hydrochlorides (9a–h) were synthesized by condensing racemic 1-(p-hydroxyphenyl)-2-aminopropan-1-ol hydrochloride (6) with substituted aryloxymethyloxiranes (8a–h) in DMF in presence of anhydrous potassium carbonate and then reacting with dry hydrogen chloride gas. They were evaluated for uterine relaxant activity in vitro on isolated rat uterus and in vivo in pregnant rats. Their cAMP releasing potential was studied using rat uterus tissue homogenates by cAMP [3H] assay and cardiac stimulant potential was evaluated in dog. All compounds exhibited potent uterine relaxant activity in vitro and produced a significant delay in the onset of labour in pregnant rats; their cAMP releasing potential was higher than isoxsuprine hydrochloride except for 9b and 9c. Finally insignificant cardiac stimulant potential was noted for these compounds when compared to isoxsuprine hydrochloride.

Design, synthesis and evaluation of racemic 1-(4-hydroxyphenyl)-2-[3-(substituted phenoxy)-2-hydroxy-1-propyl]amino-1-propanol hydrochlorides as novel uterine relaxants

Novel 1-(4-hydroxyphenyl)-2-[3-(substituted phenoxy)-2-hydroxy-1-propyl]amino-1-propanol hydrochlorides were designed based on the pharmacophore for potent uterine relaxant activity and by utilizing the principles of structural hybridization. The designed molecules were synthesized as racemates by a novel route and were evaluated for uterine relaxant activity in vitro on isolated rat uterus and in vivo in pregnant rats. Their cAMP-releasing potential was studied using rat uterus tissue homogenates by the cAMP [ 3H] assay, and cardiac stimulant potential was evaluated on isolated guinea pig right atrium. All compounds exhibited potent uterine relaxant activity in vitro and produced a significant delay in the onset of labour in pregnant rats; their cAMP-releasing potential was slightly less, while their cardiac stimulant potential was insignificant as compared to isoxsuprine hydrochloride.

Determination of isoxsuprine hydrochloride by sequential injection visible spectrophotometry

An automated sequential injection (SI) spectrophotometric method for the determination of isoxsuprine hydrochloride is described. The method is based on the condensation of aminoantipyrine with phenols (isoxsuprine hydrochloride) in the presence of an alkaline oxidizing agent (potassium hexacyanoferrate) to yield a pink colored product, the absorbance of which is monitored at 507 nm. Chemical as well as physical SI parameters that affect the signal response have been optimized in order to get better sensitivity, higher sampling rate and better reagent economy. Using the optimized aforesaid parameters, a linear relationship between the relative peak height and concentration was obtained in the range 1–60 mg l –1. The detection limit (as 3 σ value) was 0.3 mg l –1 and precision was 1.4% and 1.6% at 5 and 10 mg l –1, respectively. As compared to previous reports, wide linear range, low detection limit, and highly economical reagent consumption are the advantages of this automated method.

HPLC Determination of Ritodrine Hydrochloride in Pharmaceutical Formulations

A simple, rapid, and accurate HPLC method is described for the determination of ritodrine hydrochloride (RTH) in both pure form and pharmaceutical formulations. A Hypersil Shendon ODS column with a mobile phase of dibasic phosphate buffer and acetonitrile (75 : 25) and isoxsuprine hydrochloride were used as an internal standard. The flow rate was 1 mL min–1 and the effluent was monitored at 270 nm pH 4.0. The calibration graph is linear in the range 2–30 μg mL–1. The proposed HPLC method has been successfully employed for the determination of RTH in Yutopar tablets and injection solutions.

Isoxsuprine hydrochloride in the horse: a review

Isoxsuprine hydrochloride has been suggested for use in horses for treatment of navicular syndrome and laminitis. The drug has been shown to be a beta-adrenoreceptor antagonist with beta-adrenoreceptor agonistic properties, with both characteristics contributing to vasodilation and uterine relaxation. In addition, the drug is capable of decreasing blood viscosity and platelet aggregation. Studies have shown i.v. isoxsuprine to have a plasma half-life of <3 h with a large apparent volume of distribution. Cardiovascular effects resolve rapidly following i.v. administration, but are absent with oral dosing. Oral bioavailability is 2.2% with a high first pass effect. Isoxsuprine has an apparent affinity for melanin that may contribute to extended renal excretion. Clinical trials appear to support the use of isoxsuprine for treatment of navicular disease. However, poor bioavailability, lack of cardiovascular effects following oral administration, superficial support in clinical trials, and new evidence regarding the pathogenesis of navicular syndrome indicate that the use of isoxsuprine for treatment of navicular syndrome or laminitis is questionable at best.

Fluorimetric determination of isoxsuprine hydrochloride in pharmaceuticals and biological fluids

Two simple and highly sensitive fluorimetric methods have been developed for the determination of isoxsuprine hydrochloride in bulk, in dosage forms and in biological fluids. The first method involves the direct measurement of the native fluorescence of the drug in the concentration range 0.4–4.0 μg ml −1, the second method is based on the oxidation of isoxsuprine HCl with cerium(IV) followed by fluorimetric measurement in the concentration range 0.02–0.2 μg ml −1. The average % found were 99.9±0.78 and 100.0±0.62 for the two methods, respectively. The minimum detectability (3 S B) were 0.11 and 0.007 μg ml −1 for the two methods, respectively. The methods results showed insignificant difference with those of the official method.

Therapeutic effects of high-dose isoxsuprine in the management of mixed-type impotence

Objectives. To determine the effectiveness and safety of high-dose isoxsuprine for the treatment of mixed-type erectile dysfunction. Methods. Forty-four patients who had vasculogenic impotence diagnosed on the basis of their sexual history, physical examination, laboratory analysis, polysomnographic recording of nocturnal erections, and dynamic color Doppler sonography of the cavernosal arteries were entered into a randomized, double-blind, placebo-controlled, crossover comparison of a placebo with high-dose isoxsuprine hydrochloride (60 mg/day orally). The treatment consisted of two 30-day courses. After a 14-day washout period, the patients who initially received the placebo for 30 days switched to isoxsuprine hydrochloride for 30 days and vice versa. Erectile function, ejaculation, interest in sex, and physical examination findings were investigated before treatment and at the end of each drug period. Results. Thirty-six patients (82%) completed the entire treatment schedule. Positive clinical results (complete and partial responses) were obtained in 6 men (16.6%) at the end of the isoxsuprine phase and in 7 men (19.4%) after the placebo period. The statistical analysis disclosed no significant difference when isoxsuprine was compared with placebo ( P >0.05). Significant drug-related adverse effects occurred in the isoxsuprine group and treatment was discontinued in 2 patients. Conclusions. Isoxsuprine is no better than placebo as a first-line treatment for mixed-type erectile dysfunction.