Common Pharmaceutical Excipients Research Articles

Microwave–convective drying characteristics of pharmaceutical powders

Common pharmaceutical excipients and active ingredients, wetted with specific solvents, were dried in a combined microwave–convective system (2.45 GHz, 90 W). The drying curves showed a constant drying rate period, followed by two falling rate periods. Cross-flow air velocity had little effect on solvent evaporation rate in the initial stages; however, an increase in drying rate was observed during the falling rate period. Increasing air temperature increased the drying rate throughout the entire process, with reductions in drying time of up to 78% being observed. Average and maximum sample temperatures were found to decrease on addition of air-flow, the extent of which was dependent on material and operating conditions.

Extractive Spectrophotometric Methods for the Determination of Oxomemazine Hydrochloride in Bulk and Pharmaceutical Formulations Using Bromocresol Green, Bromocresol Purple and Bromophenol Blue

Three simple, sensitive and accurate spectrophotometric methods have been developed for the determination of oxomemazine hydrochloride in bulk and pharmaceutical formulations. These methods are based on the formation of yellow ion-pair complexes between the examined drug and bromocresol green (BCG), bromocresol purple (BCP), and bromophenol blue (BPB) as sulphophthalein dyes in acetate-HCl buffer of pH 3.6, 3.4, and 4.0, respectively. The formed complexes were extracted with dichloromethane and measured at 405 nm for all three systems. The best conditions of the reactions were studied and optimized. Beer's law was obeyed in the concentration ranges 2.0-12, 2.0-13, and 2.0-14 microg mL(-1) with molar absorptivities of 3.2 x 10(4), 3.7 x 10(4), and 3.1 x 10(4) L mol(-1) cm(-1) for the BCG, BCP, and BPB methods, respectively. Sandell's sensitivity, correlation coefficient, detection and quantification limits are also calculated. The proposed methods have been applied successfully for the analysis of the drug in pure form and in its dosage forms. No interference was observed from common pharmaceutical excipients. Statistical comparison of the results with those obtained by HPLC method shows excellent agreement and indicates no significant difference in accuracy and precision.

Thin-Layer Modeling of Microwave, Microwave-Convective, and Microwave-Vacuum Drying of Pharmaceutical Powders

Common pharmaceutical excipients and active ingredients, wetted with specific solvents, were dried under selected microwave, microwave-convective, and microwave-vacuum conditions in an experimental drying system (2.45 GHz, 90 W). The generalized drying profile was independent of drying technique and material characteristics, with a constant rate stage and two falling rate periods being observed. Moisture removal rate was, however, dependent on the drying technique (pressure and presence/absence of external heating source), and powder and solvent properties (dielectric, physical and thermal). The experimental moisture loss data were fitted to selected semi-theoretical and empirical thin-layer drying equations. The correlations were compared according to two statistical tests, namely root mean square error and reduced chi-square. The microwave, microwave-convective, and microwave-vacuum drying behaviors were adequately represented by the Page, Logarithmic, Chavez-Mendez et al. and Midilli et al. equations, with the latter providing the best description of the experimental results.

A comparison of Raman chemical images produced by univariate and multivariate data processing—a simulation with an example from pharmaceutical practice

A direct comparison of univariate and multivariate data analysis has been performed to show the effect of spectral noise on the quality of chemical images derived from hyper-spectral data cubes. A data processing approach has been developed using a numerical model, based on spectra of common pharmaceutical excipients, and then applied to a real multi-layered solid dosage formulation. The results of this study demonstrate that the multivariate analysis, which in its simplest form only de-noises data using principal component analysis (PCA), produces significantly better quality chemical images than the univariate approach, even from data sets which appear visually poor. If pure component spectra are available, ordinary least squares (OLS) regression offers even better results. The ability to de-noise spectra using these approaches impacts on Raman experimental conditions and increases information content collected per unit time. Data acquisition time, which is a rate limiting step in the production of chemical images using Raman mapping and imaging techniques, is reduced by 60% and still produces multivariate chemical images of appropriate quality with which to study pharmaceutical formulations.

Flow and Sequential Injection Manifolds for the Spectrophotometric Determination of Captopril Based on its Oxidation by Fe(III)

Two new simple and rapid methods are reported for the accurate and precise spectrophotometric determination of captopril (CPL) using flow (FI) and sequential injection (SI) analysis. The methods are based on the fast oxidation of CPL by Fe(III). The produced Fe(II) reacts with 2,2′-dipyridyl-2-pyridylhydrazone (DPPH) in acidic medium to form a colored complex which is monitored spectrophotometrically at 535 nm. Both methods allow the determination of the analyte up to 1000 mg L−1 at a sampling rate of 120 and 60 injections per hour for FI and SI, respectively. The methods are very precise [s r=0.8 and 1.2% at 500 mg L−1 CPL (n=12) for FI and SI, respectively] and the 3σ detection limits (c L=4.0 and 7.0 mg L1, respectively) are quite satisfactory. Their application to a variety of anti-hypertensive commercial pharmaceutical formulations showed excellent results (relative errors, e r, < ± 1.6% in all cases compared to an official HPLC method), while common pharmaceutical excipients were found not to interfere. Recovery experiments further verified the accuracy of the developed methods, as the percent recoveries were in the range of 98.1–102.5%.

Further investigations into the use of high sensitivity differential scanning calorimetry as a means of predicting drug–excipient interactions

The early prediction of drug–excipient incompatibility is vital in the pharmaceutical industry to avoid costly material wastage and time delays. We report here on the use of high sensitivity differential scanning calorimetry (HSDSC) to examine the compatibility between an experimental drug (Drug A) and common pharmaceutical excipients. Short-term HSDSC experiments (up to 25 h) indicated that Drug A was stable in the presence of moisture and was compatible with both lactose monohydrate and magnesium stearate in the dry state, but showed degradation in the presence of magnesium stearate and water in combination. These results agreed with conventional stability studies, in which extensive degradation was observed in the Drug A–magnesium stearate system after storage at 40 °C/75% RH for 4 weeks but not under other conditions. These results indicate that HSDSC may be used to examine the compatibility of experimental drugs with conventional excipients and, in particular, illustrate the importance of incorporating humidity as an experimental variable in order to fully establish the stability profile of the material under test.

Microwave Drying of Multi-component Powder Systems

The rate of uptake of microwave technology within the pharmaceutical sector has been slow due to stringent regulatory procedures and unsuccessful microwave trials. However, microwave systems offer significant energy and time savings compared with conventional dryers. Common pharmaceutical excipients, lactose, stearic acid, and active ingredients, Aspirin, Paracetamol, were wetted with water and dried within an experimental atmospheric microwave drying system (2.45 GHz, 90 W). The drying curves obtained showed a constant drying rate, followed by two falling rate periods. Two- and three-component mixtures were dried under the same conditions. The drying characteristics were found to lie between those of the pure components. Drying kinetics of samples wetted with a range of solvents (methanol, ethanol, acetone), and two-component solvent mixtures, were examined. The relative evaporation rates of the solvents showed some dependence on their dielectric properties; latent heat of vaporisation and boiling point having greater influence on drying characteristics. Clearly this research provides information vital to achieve increased acceptance of this technology within the pharmaceutical industry.

Spectrophotometric Determination of Antiallergic Drug in Bulk Powder and in Its Pharmaceutical Formulations

Two simple, rapid and selective spectrophotometric methods have been described for the determination of promethazine hydrochloride (PMH) either in pure or pharmaceutical formulations. The methods are based on the formation of a green colored product with sulphanilic acid (SPA) in presence of N-bromosuccinimide (NBS) or a red colored, chloroform soluble product with p-nitroaniline (PNA) in presence of ceric ammonium sulphate (CAS). The chromogen formed has maximum absorption at 600 nm and at 510 nm with SPA and PNA, respectively. The optimum reaction conditions and other analytical parameters are evaluated. Beer's law is valid in the concentration range of 0.5–25 μg/mL (R= 0.9983) with SPA and 2–75 μg/mL (R = 0.9981) with PNA. Molar absorptivity values as calculated from the Beer's law data are 5.54 × 103 L/mol/cm and 3.05 × 103 L/mol/cm for SPA and PNA, respectively. The results are in good agreement with those of the official method. No interference was observed from common pharmaceutical excipients.

A New Sensitive Fluorirnetric Method for the Determination of Heptaminol and Mexiletine in Pharmaceuticals

An accurate and very sensitive spectrofluorimetric method is proposed for the estimation of heptaminol (HP) and mexiletine (MX) in their pure forms and in pharlnaceutical formulations. The method is based on the reaction of these drugs with the strong fluorigenic reagent [9,1O-Dimethoxy-2-anthracenesulfonic acid sodium salt (DAS)] at pH (2.5). The formed complexes are extracted into chloroform and measured spectrofluori~netrically. The maximum wavelengths of excitation and emission spectra of heptaminol complex are 381 and 441 m, respectively. While those of mexiletine complex are 385 and 450 nrn, respectively. Heptaminol can be determined in the concentration range of 0.016-0.144 µg ml−1 and that of mexiletine in the range of 0.024-0.176 µg ml−1, when extracted from the solutions into chloroform. Different parameters affecting the reaction conditions were thoroughly studied. No interference was observed in the presence of common pharmaceutical excipients. The proposed method has been successfully applied to the analysis of commercial pharmaceutical fonnulations and the results have been statistically compared with those obtained by the reference methods.

Microwave Drying of Pharmaceutical Powders

Although the application of microwave dryers has proven successful in many industries, the uptake rate of microwave technology by pharmaceutical companies has been slow, particularly in the primary manufacturing sector. Pharmaceutical powders are temperature sensitive thus, drying conditions are primarily dictated by stringent quality criteria. The heating effect of microwaves on a material is controlled by the dielectric loss factor. The loss factors of single and two-component systems of some common pharmaceutical excipients and active ingredients were determined within an experimental atmospheric microwave drying system. Formulations with a high percentage of ammonium acetate exhibited comparatively high loss factors, whilst the Aspirin-based samples presented low loss factors. However, both were significantly less than that of water; the solvent used in this work. The global loss factor of a multi-component system was found to be dependent on the loss factors of the individual components and their relative concentrations. The effect of moisture content on dielectric properties was also examined. Results showed that the loss factor of bound moisture is significantly less than that of free water, however, as moisture content increases, the loss factor of a wetted powder approached that of pure water. The effect of agitation on the drying behaviour of the powders was also examined, with the results revealing that the rate of drying increases with increasing frequency of agitation.

Calorimetric analysis of powder compression: I. Design and development of a compression calorimeter

The heat of compression and work of compression of three common pharmaceutical excipients (Avicel PH-101, anhydrous lactose, and Starch 1500) were determined using experimental instrumentation of original design. The heat of compression was independently determined using two different temperature sensors: a tungsten wire temperature sensor positioned within the powder sample and a two-thermistor system positioned behind thin metal plates in the lower surface of the upper punch. The effective heat capacity of the sample when contained within the punch and die apparatus was determined by a simultaneous heating and compression method. An energy correction method was used to account for system heat effects. Upper and lower punch force transducers and a displacement transducer were used to determine the work of compression. In the materials studied, exothermic powder compression subprocesses outweighed the endothermic subprocesses and an overall net exotherm was observed. The rank orders of the heats of compression determined from the in-sample and in-punch temperature sensors were in agreement. This instrumentation and approach, while still being developed, is proposed as a discriminating method to characterize and quantitate fundamental powder compression behavior.

Single-Step Granulation Method with Microwaves: Preliminary Studies and Pilot Scale Results

Common pharmaceutical excipients and compounds were dried either by a simple convection method or by a combined convection and microwave method in a static bed or by a combined microwave and vacuum method in a mixed bed. A simple placebo granulation was dried by an exclusive vacuum method and by a combined microwave and vacuum method in a mixed bed. The results were compared.

Stability-Indicating Assay for Tolmetin Sodium in Solid Dosage Forms

A spectrophotometric assay for determining tolmetin sodium in pharmaceutical solid dosage forms is described. Tolmetin sodium is separated from common pharmaceutical excipients and probable degradation products. Recovery, precision and accuracy data are provided. Two TLC methods are included which can be used to monitor qualitatively the stability of aged dosage forms.

Simple and rapid determination of a new pharmaceutically active amine hydrochloride.

The quantitative analysis of a new pharmaceutically active amine hydrochloride is described. Samples are extracted with chloroform. A yellow amine-dye complex is formed by buffering a sample-bromthymol blue solution at pH 8.5 +/- 0.1 and subsequently extracted with chloroform. The complex is treated with 0.01 N NaOH to convert it back to the sodium salt of bromthymol blue, which is then measured at 615 nm in the aqueous layer. The amount of complex extracted is linearly related to the amount of amine present, from 0.020 to 0.20 mg/ml. Under the selected conditions, the compound can be determined in the presence of degradation products and there is no interference from common pharmaceutical excipients. The method is suitable for stability studies.