The Use of First-Order UV Spectroscopy to Determine Binary Mixtures of Pharmaceuticals (A) PHEH and CBOM and (B) DPHH and NPZH

Abstract

Procedures were developed for the simultaneous determination of pharmaceuticals in two-component commercial formulations by first-order derivative UV spectrophotometry. Phenylephrine hydro chloride and carbinoxamine maleate in capsules and diphenhydramine hydrochloride and naphazolixehydro hydrocloride in nasal gelly were succesfully assayed. A simple sensitive method in the usual range for the binary preparations has been developed. Average recoveries of the four compounds in the formulations under study were 100.04 ± 1.28% 101.50 ± 2.27 %, 101.59 % 1.24 % and 100.49 ± 2.59 %.     

Dexamethasone delivery to posterior segment of the eye

Due to anatomic barriers and lacrimal drainage it is difficult to obtain therapeutic drug concentrations in the posterior part of the eye after topical drug administrations. Lipophilic cyclodextrins, such as randomly methylated β-cyclodextrin (RMβCD), are known to act both as solubilizers of water-insoluble drugs in aqueous solutions and as penetration enhancers that reduce the barrier function of lipophilic membranes. The purpose of this study was to investigate the effects of RMβCD on dexamethasone delivery from aqueous eye drop solution into rabbit eyes. Dexamethasone (0.5 and 1.5% w/v) drops (50 μl) were administered to the left eye of rabbits (n = 6) and the drug levels measured in different eye tissues 2 h after administration. In aqueous humor dexamethasone levels were 1,190 ± 110 and 1,670 ± 630 ng/g (mean ± SD) after administration of the 0.5 and 1.5% dexamethasone eye drops, respectively. In the retina the levels were 33 ± 7 and 66 ± 49 ng/g, and in optic nerve 41 ± 12 and 130 ± 50 ng/g, respectively. In a previous study the dexamethasone concentration in aqueous humor after topical administration of 1.3% (w/v) dexamethasone eye drops in aqueous 2-hydroxypropyl-β-cyclodextrin (HPβCD) solution was determined to be 320 ± 230 ng/g and 66 ± 20 ng/g after administration of Maxidex^® eye drops. Both the hydrophilic HPβCD and the lipophilic RMβCD enhance topical dexamethasone delivery into the eye, but of the two, the lipophilic RMβCD results in higher dexamethasone concentrations.     

UHPLC Study on the Degradation Profiles of Olopatadine Hydrochloride in Eye Drops Subjected to Heat and Filtration Methods of Sterilisation

A validated ultra-high performance liquid chromatography (UHPLC) method has been proposed, validated and used for the determination of olopatadine hydrochloride degradation products in olopatadine 1 mg mL^?1 eye drops solution under the influence of two different sterilisation methods, heating and filtration, with good precision and accuracy. We found that the heat sterilization method yields a higher content of olopatadine hydrochloride degradation products in eye drops compared to unsterilized drug product or drug product sterilized by filtration, except for α-hydroxy olopatadine impurity, which remains stable with time and applied sterilization method. Contents of olopatadine related compound B shows a higher increase (from <0.005 to 0.044 %) when sterilised by heating than when subjected to aging and sterilization by filtration (increase up to 0.011 %). Similarly, total amount of all impurities is also increased from 0.13 to 0.49 % when the drug product is sterilised by heating instead of filtration (up to 0.39 %). Content of olopatadine related compound B and of all impurities is increased by aging, probably through thermal and oxidative degradation. Forced degradation studies were correlated with the sterilisation study and possible degradation pathways were identified. Olopatadine shows strong degradation under oxidative and moderate degradation under photolytic environment, with the olopatadine related compound B as the main degradation product. Sterilization of eye drops solution by filtration is recommended.     

Stability-Indicating Method For The Determination Of N-Desmethyldiazepam And Simultaneous Determination Of Its Degradation Products

Abstract

A simple, direct and sensitive spectrophotometric method for the determination of the intact N-desmethyldiazepam in the presence of its degradation products, 2-amino-5-chlorobenzophenone and glycine, is developed. The proposed procedure is based on direct measurement of the absorbance of its acidified methanolic solution at 361 nm. The procedure determines 8–56 mcg ml^?1 of N-desmethyldiazepam with an accuracy of 100.2 ± 0.51%. The proposed procedure retains its accuracy in presence of up to 80% of the different degradation products. The procedure is applied successfully for the determination of N-desmethyldiazepam in bulk powder, tablets and drops.

Simultaneous determination of the different degradation products in the presence of the parent drug is also described. Thus, 2-amino-5-chlorobenzophenone is determined by direct measurement of its methanolic solution at about 380 nm, with an accuracy of 100.4 ± 0.42%. Glycine is determined colorimetrically using ninhydrin reagent in presence of pyridine, with an accuracy of 99.5 ± 0.78%.     

Colorimetric and Bromometric Determination of Pirbuterol Hydrochloride

Abstract

Two proposed methods are reported for the quantitation of pirbuterol hydrochloride, namely, (i) colorimetric and (ii) titrimetric methods. The colorimetric method is based on coupling betweem diazotized sulphanilamide and pirbuterol hydrochloride. Under the optimum conditions studied, the coupling product exhibits a maximum at 440 nm. Linear relation between absorbance, A, and concentration of pirbuterol hydrochloride is in the range 5–40 μgml^?1. The mean percentage obtained for capsules (Exirel^R ?15 mg) was 100.8 ± 0.7 whereas mean percentage recovery obtained for the authentic drug was 100.5 ± 0.8.

The titrimetric procedure involves bromination of authentic pirbuterol in acid medium and residual titration of excess bromine. The stoichiometry of the reaction was investigated and infra-red analysis, of the bromoderivative was carried out. When applied to capsules the bromometric method gave mean percentage of 100.18 ± 2.25.     

A green chemistry approach towards synthesizing hydrogel for sustained ocular delivery of brinzolamide: In vitro and ex vivo evaluation

Brinzolamide is a carbonic anhydrase inhibitor used in the eye drop form for the treatment of glaucoma. It requires frequent dosing to attain therapeutic concentration. Therefore, this study aimed to prepare sustained ocular drug delivery of brinzolamide. The objective of the study was to prepare a hydrogel loaded with a nanostructured lipid carrier (NLC) of brinzolamide. The hydrogel was prepared by a green synthesis approach using genipin as a natural crosslinking agent and polymers such as carboxymethyl chitosan and poloxamer 407. The melt emulsification-ultra sonication method was used to prepare a nanostructured lipid carrier of brinzolamide, which was loaded into a hydrogel using a swelling and loading method. The NLC formulation has shown small particle sizes of 111.20 ?± ?2.15 ?nm, polydispersity index of 0.280 ?± ?0.005 and % entrapment efficiency of 82.16% ?± ?0.14%. The NLC-loaded hydrogels of brinzolamide formulations were studied for swelling properties and showed temperature and pH-responsive swelling behavior. The optimized hydrogel formulation has been studied for in vitro drug release and showed drug release for a longer duration (24 ?h) than marketed eye drops (8 ?h). In an ex vivo study, hydrogel formulations showed transcorneal permeability 4.54 times greater than marketed eye drops. The hydrogel formulation of brinzolamide produced by the green synthesis method has shown sustained-release properties with no sign of ocular irritation. Hence, the hydrogel of brinzolamide-loaded NLC would be the potential drug delivery approach in the near future for sustained ocular drug delivery in glaucoma management.     

Construction and Validation of New Electrochemical Carbon Nanotubes Sensors for Determination of Acebutolol Hydrochloride in Pharmaceuticals and Biological Fluids

A simple, rapid and a highly selective method for direct electrochemical determination of acebutolol hydrochloride (AC) was developed. The developed method was based on the construction of three types of sensors conventional polymer (I), carbon paste (II) and modified carbon nanotubes (MCNTs) carbon paste (III). The fabricated sensors depend mainly on the incorporation of acebutolol hydrochloride with phosphotungstic acid (PTA) forming ion exchange acebutolol‐phosphotungstate (AC‐PT). The performance characteristics of the proposed sensors were studied. The sensors exhibited Nernstian responses (55.6 ± 0.5, 57.14 ± 0.2 and 58.6 ± 0.4 mV mol L^?1) at 25 °C over drug concentration ranges (1.0 × 10^?6‐1.0 × 10^?2, 1.0 × 10^?7‐1.0 × 10^?2 and 5.0 × 10^?8‐1.0 × 10^?2 mol L^?1 with lower detection limits of (5.0 × 10^?7, 5.0 × 10^?8 and 2.5 × 10^?8 mol L^?1 for sensors (I), (II) and (III), respectively. The influence of common and possible interfering species, pharmaceutical additives and some related pharmacological action drugs was investigated using separate solution method and no interference was found. The stability indicating using forced degradation of acebutolol hydrochloride was studied. The standard addition method was used for determination of the investigated drug in its pharmaceutical dosage forms and biological fluids. The results were validated and statistically analysed and compared with those from previously reported methods.     

S-OXIDATION PRODUCTS OF ALKYLTHIOAMPHETAMINES

ABSTRACT

The preparation of the sulfoxides and the sulfones of two centrally active alkylthioamphetamine salts, (±)-1-(4-methylthiophenyl)-2-aminopropane hydrochloride (2) (MTA · HCl) and (±)-1-(2,5-dimethoxy-4-ethylthiophenyl)-2-aminopropane hydrochloride (7) (ALEPH-2 · HCl), is described.     

Stability-Indicating Method for the Determination of Hydrochlorothiazide,Benzydamine Hydrochloride and Clonazepam in the Presence of Their Degradation Products

Abstract

Spectrophotometric, colorimetric and densitometric methods for the determination of hydrochlorothiazide, benzydamine hydrochloride and clonazepam in the presence of their degradation products are described. Hydrochlorothiazide was determined in the presence of its degradation products methoxyhydrothiazide, hydroxyhydrothiazide and 5-chloro-2,4-disulfonamidoaniline applying the first and second derivative spectrophotometer at 278.8 nm and 254.4 nm, respectively, while benzydamine hydrochloride was determined in the presence of its toxic photodegradation products 5-hydroxybenzydamine and 2-B-dimethylaminopropyl-l-benzylindalolin-3-one colorimetrically using the acid dye bromophenol red and measuring the absorbance of the chloroform solution of the ion-pair formed at 425nm. Clonazepam was determined densitometrically in the presence of its degradation products carbostyril and 2-amino-2-chloro-5-nitrobenzophenone. The suggested methods determine hydrochlorothiazide, benzydamine hydrochloride and clonazepam in the presence of degradation products with mean accuracies of 99.57±0.51%, 100.04±0.41%, 100.03±0.21% and 99.84±0.34%, respectively. The proposed methods are suitable for stability testing in bulk powder and in pharmaceutical preparations.     

A Sensitive Spectrophotometric Method for the Determination of Some Imidazoline Derivatives by 2,6-Dichlorophenol-Indophenol

Abstract

A new and highly sensitive method is presented for the spectrophotometric determination of four imidazoline derivatives: antazoline hydrochloride, tolazoline hydrochloride, xylometazoline hydrochloride and naphazoline nitrate. The method is based on the reaction of the corresponding drug base with 2,6 - dichlorophenol -indophenol (DGPIP) in chloroform to give a blue chromogen exhibiting a maximum at 588 - 603nm. The method could be applied for the quantitative determination of the above drugs either pure or in their pharmaceutical preparations (tablets and nasal drops). The results obtained are accurate and have good reproducibility.     

Simplex Optimization of Densitometer Parameters for Maximum Precision in Quantitative Thin Layer Chromatography

Abstract

Simplex optimization was employed for the selection of densitometer slit width and wavelength settings to maximize the reproducibility of the determination of diphenhydramine hydrochloride and pseudoephedrine hydrochloride in Benadryl-D^IM capsules by thin layer chromatography. The two densitometer parameters were simultaneously adjusted in a systematic manner to minimize the sum of the squares of the relative standard deviations of the respective peak areas from the two active compounds on a developed thin layer chromatographic plate. The optimization process was followed graphically and resulted in the rapid establishment of a single set of densitometer parameters giving peak areas with relative standard deviations of less than 1% for each of the active components in the formulation.     

Electrochemical and Spectral Behaviour of a New Cardiotonic Drug (Sulmazole)

Abstract

Spectrophotometric and electrochemical properties of sulmazole are studied. The acid-base constants are calculated (pk_a1 = 3.88 ± 0.04 and pK_a2 = 11.39 ± 0.06).

The drug can be spectrophotometrically determined between 4.01 × 10^?5 M and 4.02 × 10^?6 M at 327 nm with relative errors lower than 0.4 % and relative standard deviations lower than 2.0 %.

The electrochemical reduction of sulmazole was investigated by DCT, DP polarography and cyclic voltammetry. Reduction of the drug was carried out in two irreversible steps using Britton-Robinson bu ffer (pH < 7). Half-wave potentials for 1.53 × 10^?4 M sulmazole at pH 2.5 are -0.825 V and -0.995 V (versus Ag/AgCl/3M KC1).

Two different methods for determination of sulmazole in tablets are proposed.     

Reversed-Phase High Performance Liquid Chromatographic and Thin Layer Chromatographic Methods for the Simultaneous Determination of Benazepril Hydrochloride and Hydrochlorothiazide in Cibadrex Tablets

ABSTRACT

Two procedures were developed for simultaneous determination of benazepril hydrochloride (I) and hydrochlorothiazide (II) in pure, laboratory made mixtures and in pharmaceutical dosage form “Cibadrex tablets® using reversed phase high performance liquid chromatographic and thin layer chromatographic methods.

For reversed phase HPLC, a new very sensitive, rapid, selective method was developed. The linearity ranges were 32-448 ng/20 μl and 40-560 ng/20 μl for benazepril hydrochloride and hydrochlorothiazide, respectively. The corresponding recoveries were 99.38 ± 1.526 and 99.2 ± 1.123.

The minimum detection limits were 7 ng/20 μl and 14 ng/20 μl for benazepril hydrochloride and hydrochlorothiazide respectively.

On the other hand, a new, simple, sensitive and fast thin layer chromatographic scanning densitometric method was developed for simultaneous determination of benazepril hydrochloride and hydrochlorothiazide using ethyl acetate: methanol: ammonia (85: 20: 10 v/v) as the developing system. The R_f values were 0.33 & 0.68 for benazepril hydrochloride and hydrochlorothiazide respectively. The minimum detection limit obtained was 0.12 μg/spot for benazepril hydrochloride and 0.24 μg/spot for hydrochlorothiazide. The mean percentage recoveries were 100.04 ± 1.102 and 99.31 ± 1.009 for benazepril hydrochloride and hydrochlorothiazide respectively.

The two proposed methods were simple, precise, sensitive and could be successfully applied for the determination of pure, laboratory made mixtures and pharmaceutical dosage forms. The results obtained were compared with those obtained by A ^1%.     

Spectrophotometric Determination of Diphenadione Via its Metal Complexes

Abstract

Spectrophotometric procedure is described for the quantitative determination of diphenadione [2-(diphenylacetyl)-1,3-indandione], based on direct spectrophotometric measurements of the absorbances of its iron (III), iron (II) and cobalt (II), metal complexes at 488 nm, 505 nm and (334 nm, 372 nm), respectively. The drug reacts with metals in the ratio of 3:1 and 2:1 for iron (III) and for both iron (II) and cobalt (II) respectively. The obtained complexes have apparent molar absorptivities of 1.48 × 10³ 1 mol^?1 cm^?1, 0.714 × 10³ 1 mol^?1cm^?1 and (1.70 × 10³ 1 mol^?1cm^?1, 1.93 × 10³ 1 mol^?1cm^?1) for iron (III), iron (II) and cobalt (II) complexes, respectively. The procedure is suggested for the determination of 51–400 μg.ml^?1 diphenadione via the iron (II) complex and 35–170 μg.ml^?1 diphenadione via both cobalt (II) and iron (III) complexes. The suggested procedure has accuracies of 99.79 ± 0.67%, 99.64 ± 0.37% and (100.09 ± 0.53%, 99.99 ± 0.42%) for the metal complexes of iron (III), iron (II) and cobalt (II), respectively.     

Determination of Pseudoephedrine Hydrochloride in Some Pharmaceutical Drugs by Potentiometric Membrane Sensor Based on Pseudoephedrine–Phosphotungstate Ion Pair

Abstract

An ion-selective electrode (ISE) was developed for the rapid determination of pseudoephedrine hydrochloride (PSEHCl) in pharmaceutical preparations. The electrode incorporates a PVC membrane with a pseudoephedrine–phosphotungstate ion pair complex. The influences of membrane composition, temperature, pH of the test solution, and the interfering ions on the electrode performance were investigated. The sensor exhibits a Nernstian response for pseudoephedrine hydrochloride ions over a relatively wide concentration range (1.0 × 10^?1 to 1.0 × 10^?5 mol L^?1) with a slope of 56.2 ± 0.5 mV per decade at 25°C. It can be used in the pH range 4.0–10.5. The isothermal temperature coefficient of this electrode amounted to 0.0009 V/°C. The membrane sensor was successfully applied to determination of PSEHCl in its tablets and syrup.     

Disposable screen-printed sensors for determination of duloxetine hydrochloride

A screen-printed disposable electrode system for the determination of duloxetine hydrochloride (DL) was developed using screen-printing technology. Homemade printing has been characterized and optimized on the basis of effects of the modifier and plasticizers. The fabricated bi-electrode potentiometric strip containing both working and reference electrodes was used as duloxetine hydrochloride sensor. The proposed sensors worked satisfactorily in the concentration range from 1.0 × 10^-6-1.0 × 10^-2 mol L^-1 with detection limit reaching 5.0 × 10^-7 mol L^-1 and adequate shelf life of 6 months. The method is accurate, precise and economical. The proposed method has been applied successfully for the analysis of the drug in pure and in its dosage forms. In this method, there is no interference from any common pharmaceutical additives and diluents. Results of the analysis were validated statistically by recovery studies.     

Surfactant-to-Dye Binding Degree Method for the Determination of Morphine Hydrochloride and Codeine Phosphate in Pharmaceuticals

Abstract

The surfactant-to-dye binding degree method was used to determine morphine hydrochloride and codeine phosphate. Neutral red and bis(2-ethylhexyl) sulfosuccinate (AOT) were used as the dye and surfactant, respectively, to form dye–surfactant aggregates. Addition of the drug resulted in a decrease in the dye–surfactant binding degree, proportional to the drug concentration. This was measured by monitoring the absorbance changes of the dye at 532 nm. Under the optimum conditions, the calibration graphs were linear up to 32 and 28 µg mL^?1 for morphine hydrochloride and codeine phosphate, respectively, with the corresponding detection limits of 0.40 and 0.35 µg mL^?1.     

Kinetic Spectrophotometric Determination of Ritodrine Hydrochloride in Dosage Forms

A simple and sensitive kinetic method was developed for the determination of ritodrine hydrochloride in pharmaceutical preparations. The method is based upon a kinetic investigation of the oxidation reaction of the drug with alkaline potassium permenganate at room temperature for a fixed 12.5 min; the absorbance of the colored permenganate ion was measured at 609 nm. The absorbance concentration plots were rectilinear over the range of 1.6–11.2 μg mL^?1 (r = 0.9992) with a minimum detectability of 0.096 μgmL^?1 (2.88 × 10^?7 M). The different experimental parameters affecting the development and stability of color were carefully studied and optimized. The determination of ritodrine hydrochloride by the fixed concentration and rate constant methods is also feasible with the calibration equations obtained, but the fixed time method has been found to be more applicable. The proposed method was applied successfully to the determination of ritodrine hydrochloride in tablets and ampoules with average recoveries of 100.37 ± 0.93% and 100.42 ± 0.87%, respectively. The results obtained were in good agreement with those obtained using a reference method for comparison. A proposal of the reaction pathway is also presented.     

Recognition in water of bioactive substrates by a sulphonato p-tert-butylcalix[5]arene

The molecular recognition in water of neurotransmitter monoamine and trace amine hydrochlorides by p-tert-butylcalix[5]-arene 1 – bearing 4-sulphonatobutoxy groups at the lower rim – has been investigated. According to ¹H NMR measurements, the hydrophobic cavity of receptor 1 best binds tyramine hydrochloride, K_a = 5370 ± 870 M^? 1.     

First-Derivative Spectrophotometric Determination of a Mixture of Pirbuterol Hydrochloride and Butorphanol Tartrate

Abstract

Vierordt's method, its modified version and the first derivative method have been applied for the simultaneous determination of butorphanol tartrate and pirbuterol hydrochloride in laboratory mixtures of authemtic and dosage forms. The first derivative spectrophotometric method yields accurate and reprodeucible results for both drugs. Mean percent recoveries for butorphanol tartrate and pirbuterol hydrochloride in dosage forms were 100.54±0.84 and 100.42±1.27, respectively. Virrordt's method and its modified version have given unreliable results; the reasons behind have been discussed.