Laura D. Simionato

Dissolution Stability Study of Cefadroxil Extemporaneous Suspensions

Dissolution studies have become matter of great significance because, in most cases, drug dissolution is the rate-limiting step in the absorption process. As occurs with solid oral dosage forms, heterogeneous disperse systems (suspensions) could also have some problems with their in vitro dissolution. The dissolution behavior of four different brands of cefadroxil extemporaneous suspensions available in the Argentinian market was evaluated. The deliverable volume, pH, visual appearance, uniformity of dosage units, and assay were also studied. Powders for oral suspension were stored under different aging conditions. Samples at room temperature and refrigerated conditions were taken at several time points to carry out the dissolution stability study during the expiration period of the reconstituted form. Marked differences were recorded with respect to in vitro dissolution behavior between the different products under evaluation.

Effect of Accelerated-Aging Conditions on the Dissolution Stability of Ciprofloxacin Tablets

The aim of the present study was to evaluate and compare the influence of accelerated-aging conditions on the drug c ontent and in vitro dissolution stability of eleven different ciprofloxacin (CIP) 500-mg tablets obtained from pharmacies and hospitals in Argentina. CIP, a Class II/IV drug in the Biopharmaceutics Classification System, is a fluoroquinolone antibiotic agent used in the treatment of bacterial infections. CIP content was evaluated following USP (1) specifications. Dissolution efficiency (DE) was calculated from dissolution profiles that were performed according to the British Pharmacopoeia monograph for CIP tablets (2). This determination was performed at time zero and after three (3M) and six months (6M) of storage, according to ICH accelerated-aging conditions (40 °C/75% RH). Each formulation was compared with the reference at the specified times, using ANOVA in terms of DE and similarity factor f2. Furthermore, ANOVA for DE values was used to evaluate the effect of aging conditions on the dissolution stability within each formulation. Although the storage conditions examined in the study affected the dissolution behavior of all CIP formulations, they did not have a significant effect on chemical stability, with the exception of one formulation that showed undesirable performance in both chemical and dissolution stability.

Determination of moisture content in lyophilized mannitol through intact glass vials using NIR micro-spectrometers

Determination of moisture content in lyophilized solids is fundamental to predict quality and stability of freeze-dried products, but conventional methods are time-consuming, invasive and destructive. The aim of this study was to develop and optimize a fast, inexpensive, noninvasive and nondestructive method for determination of moisture content in lyophilized mannitol, based on an NIR micro-spectrometer instead of a conventional NIR spectrometer. Measurements of lyophilized mannitol were performed through the bottom of rotating glass vials by means of a reflectance probe. The root mean standard error of prediction (RMSEP) and the correlation coefficient (R2pred), yielded by the pre-treatments and calibration method proposed, was 0.233% (w/w) and 0.994, respectively.

STABILITY INDICATING HPLC METHOD FOR THE DETERMINATION OF BENZOPHENONE-3 AND AVOBENZONE IN COSMETIC FORMULATIONS

An accurate, simple, and reproducible liquid chromatographic method was developed and validated for the determination of benzophenone-3 and avobenzone in a cosmetic formulation. The analyses were performed at room temperature on a reverse-phase C18 column (Inerstil ODS-3) (250 × 4.6 mm, 5 µm). The mobile phase, which consisted of methanol:water (95:5) and pH 3.2 adjusted with 85% of phosphoric acid, was pumped at a constant flow rate of 1 mL/min. Detection was performed on a UV detector at 315 nm. The method was validated in terms of linearity, precision, accuracy, and specificity by forced decomposition of benzophenone-3 and avobenzone using acid, base, water, hydrogen peroxide, heat, and light. The response of was linear in the range 0.08 to 0.24 mg/mL and 0.04 to 0.12 mg/mL for benzophenone-3 (r2 = 0.9984), and avobenzone (r2 = 0.9925), respectively. The relative standard deviation values for intra- and inter-day precision studies were 0.81 and 0.91 for benzophenone-3 and 1.57 and 1.13 for avobenzone. Recoveries ranged between 99.58 and 101.39 for benzophenone-3 and 98.63 and 102.05 for avobenzone.

Comparison between the dissolution profiles of nine meloxicam tablet brands commercially available in Buenos Aires, Argentina

In this work, the dissolution profiles of nine meloxicam tablet brands marketed in Argentina have been evaluated. As meloxicam is a Class 2 Biopharmaceutical Classification System (BSC) drug, interchangeability between commercial products must be demonstrated through in vivo bioequivalence studies. However, in our country, such studies remain to be performed. Dissolution studies have been performed according to USP 38 and evaluated by fitting experimental data to the zero and first-order, the Hixson-Crowell, the Higuchi, and the Weibull model-dependent methods. To test the pertinence of these release models, the Akaike Information Criteria (AIC) were used. All brands satisfied the dissolution profiles (phosphate buffer, pH 7.5) established in the USP. The comparison between the dissolution profiles was carried out by model-dependent and model-independent methods. The Weibull model provided the best kinetic curve adjustment. Brands I, II, IV and VI had the best fitting, with the maximum determination coefficient and the smallest AIC values. Model-independent methods included ratio test and the fit factors. The Dissolution Efficiency (DE) and Mean Dissolution Time (MDT) were analysed with ANOVA and the DGC method. In both cases, brand I did not show similarity with the rest of the brands. Using fit factors, only brands I, II and V were similar to each other. Significant differences were found among the in vitro dissolution profiles of meloxicam tablets belonging to the nine brands. As meloxicam is a class 2 BCS drug, interchangeability between commercial products must be demonstrated through in vivo bioequivalence studies. However, in Argentina, such studies remain to be performed. Our results demonstrate that caution must be exercised as regards interchangeability of generic products.

Comparison of Dissolution Profiles of Furosemide Tablets Available in the Argentinian Market

In this work dissolution profiles of furosemide tablets of nine commercial products marketed in Argentine were evaluated. All brands fulfill the specifications of dissolution test of USP. Comparison of dissolution profiles were carried out by model-dependent and model independent approaches. Results obtained via model-dependent approach show a first order drug release mechanism especially for Brand I (reference) and Brand IV. Results obtained via model-independent approach show that there was not significant difference in Dissolution efficiency between the reference product and Brands II, III and IV and in Mean dissolution time between the reference product and Brands II, III, IV and V. Using fit factors, only Brands I and III were similar.

Validation of Simultaneous Volumetric and HPLC Methods for the Determination of Pridinol Mesylate in Raw Material

Simple, sensitive, and economical simultaneous volumetric and HPLC methods for the determination of pridinol mesylate in raw material have been developed. The volumetric method is based on the reaction of pridinol with sodium lauryl sulphate in diluted sulphuric acid. Dimethyl yellow was used as indicator to detect the end point of the titration in aqueous/organic layer. The HPLC method for the determination of pridinol mesylate employs a reverse phase C18 column at ambient temperature with a mobile phase consisting of acetonitrile: 0.05 M potassium dihydrogen phosphate, pH adjusted to 5.0 (1 : 2, v/v). The flow rate was 0.8 mL/min. Quantitation was achieved with UV detection at 258 nm based on peak area. Both methods were found to be suitable for the quality control of pridinol mesylate in raw material.

A Comparative In Vitro Assay of Drug Release Performance of Pyridostigmine Bromide Tablets

Myasthenia gravis is an autoimmune disease that destroys key components of the neuromuscular system. The most common therapy uses reversible inhibitors of cholinesterase activity, such as pyridostigmine bromide (PB). The nature of this illness implies that we must be sure that all available PB immediate-release tablets produce the same therapeutic response. The aim of this study was to analyze PB immediate-release formulations provided by pharmacies in MERCOSUR countries A, B, and C. The formulations, which were produced in different manufacturing plants of the same multinational company, were analyzed following USP 29 specifications. The products fulfilled the assay, uniformity of dosage units, and dissolution test in S2 stage. Dissolution profiles were carried out following EMEA and FDA regulations, and the similarity factor (f2) was applied to A and C but not B, as this one did not fulfill the dissolution requirements. Pyridostigmine bromide tablets from countries A and C are considered to be similar and could be interchangeable. Formulation B exhibited such different dissolution behavior that its interchangeability is discouraged, as well as its introduction in countries A and C from the manufacturing country B.