Compounded Capsules Research Articles

DESENVOLVIMENTO E VALIDAÇÃO DE MÉTODO ANALÍTICO PARA DETERMINAR O DOSEAMENTO DE CINARIZINA EM CÁPSULAS MAGISTRAIS

Background: Cinnarizine is a brain vasodilator used in labyrinth diseases, a disorder characterized by dizziness, gait deviations, or falling. The quality control of compounded capsules containing cinnarizine is limited. Because of the difficulty accessing official pharmacopeia monographs of this drug, there is a need to describe an analytical method that is reliable and safe to perform the quantitative determination of cinnarizine in capsules. Aim: This work aims to develop and validate an analytical method to determine cinnarizine assay in capsules by spectrophotometry in the UV region that is easy to perform, low cost, and offers reliability in the dosage results. Methods: The RDC nº. 166, of 24 July 2017, of the National Health Surveillance Agency, was used as the guide for validating analytical methods. Results and Discussion: The proposed method was linear in the range of 5.833 to 10.833 μg mL-1 and presented similar results of linear and Person correlation coefficient (0.999), selectivity/specificity (0.14 %), detection limits (130, 20 ng/mL), and quantification (260, 40 ng/mL) at 251 nm. The accuracy results (DPR Rep. accuracy: 2.89 %; DPR Inter. accuracy: 1.07 %) and precision (CQB= 99.96 %, CQM= 100.02 %, and CQA= 100.06 %) complied with the validation parameters. The robustness has been proven, and the analytical method does not vary significantly from small deliberations. After validation, the assay of cinnarizine in capsules of pharmacies of the retail trade of Barra do Garças - MT was determined. The results were found to comply with Farmacopéia Brasileira 6th Edition requirements. Conclusions: The validated analytical method proved to be linear, specific, accurate, and robust and allows the determination of the dosage of cinnarizine in compounded capsules in a simple way, with low cost, and provides reliable results.

Influência dos excipientes nas propriedades de fluxo e dissolução de cápsulas manipuladas de aciclovir.

Acyclovir (ACV) is used to treat infectious diseases caused by the herpes virus. Its high cohesiveness makes encapsulation difficult and compromises the final quality of the compounded product. The aim of this work was to select excipients capable of improving the flow properties of ACV in relation to the preparation of compounded capsules with 400 mg of the active pharmaceutical ingredient (API) and to guarantee the recommended dissolution rate. Eight blends of excipients (A – H) distinctly composed of colloidal silicon dioxide (DSC), sodium starch glycolate, purified talc, hydroxypropyl cellulose and microcrystalline cellulose (MCC) were evaluated for flowability, where four of them (A, B, C and E) were selected to compose the capsule formulations because they exhibit the lowest values referring to the Hausner Factor and the Carr index. The ACV assay showed purity content of 99.3%. Although all formulations have approved the weight determination criteria, only capsules containing ACV and E blend (DSC:MCC) achieved the specified dissolution rate. This indicates that the association of such excipients provided appropriate porosity to the ACV particles through the reduction of interparticular cohesion, a fact that favored the penetration of water in the packaged powder blend. Finally, it is suggested that the production of compounded capsules containing ACV 400 mg be carried out employing capsule shells of size No00 with approximately 190 mg of DSC and MCC (2.5:97.5) in order to aid the flow of the API, provide adequate weight uniformity and achieve the desired dissolution rate to promote an effective antiviral therapy

Physicochemical stability of compounded midazolam capsules over a one-year storage period

Abstract Objectives In patients suffering from chronic liver disease, the hepatic metabolism of drugs is perturbed and the metabolic capacity is difficult to assess. Midazolam could be used as a phenotypical probe to predict the metabolic capacity of CYP3A to adjust dosages of drug substrates of this cytochrome. In this context, a prospective clinical trial is going to be conducted in our institution and a hospital preparation of midazolam capsules suitable for the clinical trial was developed. The objective of the present work was to assess the physicochemical stability of the formulation over 12 months to set shelf life. Methods Three batches of 1 mg capsules were prepared using midazolam hydrochloride and microcrystalline cellulose as a diluent. The capsules were stored at ambient temperature and protected from light. To measure the evolution of the capsules content, a stability-indicating high-performance liquid chromatography (HPLC) method was developed with ultraviolet (UV) detection at 254 nm. Data were confirmed using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method. Results After one year, midazolam hydrochloride content remained higher than 95% of the initial concentration in capsules. Conclusions The results show that 1 mg midazolam capsules are stable for 12 months at room temperature and under dark conditions.

Potential differences in antidepressant effects of oral ketamine liquid suspension versus compounded capsules

Potential differences in antidepressant effects of oral ketamine liquid suspension versus compounded capsules

Analysis of lomustine drug content in FDA-approved and compounded lomustine capsules.

OBJECTIVE To determine the lomustine content (potency) in compounded and FDA-approved lomustine capsules. DESIGN Evaluation study. SAMPLE 2 formulations of lomustine capsules (low dose [7 to 11 mg] and high dose [40 to 48 mg]; 5 capsules/dose/source) from 3 compounders and from 1 manufacturer of FDA-approved capsules. PROCEDURES Lomustine content was measured by use of a validated high-pressure liquid chromatography method. An a priori acceptable range of 90% to 110% of the stated lomustine content was selected on the basis of US Pharmacopeia guidelines. RESULTS The measured amount of lomustine in all compounded capsules was less than the stated content (range, 59% to 95%) and was frequently outside the acceptable range (failure rate, 2/5 to 5/5). Coefficients of variation for lomustine content ranged from 4.1% to 16.7% for compounded low-dose capsules and from 1.1% to 10.8% for compounded high-dose capsules. The measured amount of lomustine in all FDA-approved capsules was slightly above the stated content (range, 104% to 110%) and consistently within the acceptable range. Coefficients of variation for lomustine content were 0.5% for low-dose and 2.3% for high-dose FDA-approved capsules. CONCLUSIONS AND CLINICAL RELEVANCE Compounded lomustine frequently did not contain the stated content of active drug and had a wider range of lomustine content variability than did the FDA-approved product. The sample size was small, and larger studies are needed to confirm these findings; however, we recommend that compounded veterinary formulations of lomustine not be used when appropriate doses can be achieved with FDA-approved capsules or combinations of FDA-approved capsules.

Pharmaceutical Evaluation of Compounded Trilostane Products

Compounded trilostane capsules (15 mg, 45 mg, or 100 mg) were purchased from eight pharmacies and assayed for content and dissolution characteristics. Capsules made in-house containing either inert material or 15 mg of the licensed product and proprietary capsules (30 mg and 60 mg) served as controls. Findings were compared with regulatory specifications for the licensed product. Altogether, 96 batches of compounded trilostane and 16 control batches underwent analysis. In total, 36 of 96 (38%) compounded batches were below the acceptance criteria for content. The average percentage label claim (% LC) for each batch ranged from 39% to 152.6% (mean, 97.0%). The range of average % LC for the controls was 96.1-99.6% (mean, 97.7%). The variance in content of the purchased compounded products was substantially greater than for the controls (234.65 versus 1.27; P<0.0001). All control batches exceeded the acceptance criteria for dissolution, but 19 of 96 batches (20%) of purchased compounded products did not. Mean percent dissolution for the purchased compounded products was lower than for controls (75.96% versus 85.12%; P=0.013). These findings indicate that trilostane content of compounded capsules may vary from the prescribed strength, and dissolution characteristics may not match those of the licensed product. The use of compounded trilostane products may therefore negatively impact the management of dogs with hyperadrenocorticism.

Development and in vitro evaluation of extended-release theophylline matrix capsules

Polymers like cellulose (MethocelTM K100MPRCR, K15MPRCR and E4MCR) at different proportions (15-35%) were used to slow the release of theophylline (100 mg) from capsules. Volumetric method for powder filling capsules was used to prepare the capsules. Drug release from capsules was performed using apparatus 1, at 100 rpm and 900 mL of intestinal medium without enzymes (pH 7.5), at 37 °C, following the USP 28th ed. (Test 8). Dissolution profiles were compared to two batches of commercial extended-release capsules. Capsules compounded with 35% (wt/wt) of MethocelTM E4MCR showed dissolution profile according to the official especifications. Similar results were reproduced with other ten compounded batches. Commercial extended-release capsules containing theophylline pellets (100 mg) showed quick drug release when submitted to the same test, indicating that, in these conditions, the capsules did not show prolonged release. Mathematical models like zero-order, first-order and Higuchi were applied in kinetic studies of theophylline release from the compounded capsules. Polymers were efficient to control the release of theophylline in capsules involving diffusion and erosion as mechanisms, and that first-order model was the best fitted one for theophylline matrix capsules. These results support that compounded extended-release capsules can be prepared, since the drug release tests can be done.

Development and Validation of a Reversed-Phase HPLC Method for the Determination of Deflazacort in Pharmaceutical Dosage Forms

A reversed-phase high-performance liquid chromatographic method has been developed and validated for quantitative determination of deflazacort in tablets and in compounded capsules. Isocratic chromatography was performed on a C18 column with acetonitrile–water 80:20 (v/v) as mobile phase at a flow rate of 1.0 mL min−1. UV detection was at 240 nm. The linearity of the method was good (r > 0.999), as also were intra-day and inter-day precision (RSD 98%). The method was also validated for specificity and robustness. The results showed the proposed method is suitable for its intended use.

Liquid Chromatographic Determination of Cetirizine in Oral Formulations

The development and validation of a reversed-phase liquid chromatographic (LC) method for the determination of cetirizine dihydrochloride in oral formulations are described. An isocratic LC analysis was performed on a reversed-phase C18 column (250 x 4.6 mm id, 5 microm particle size). The mobile phase was 1% orthophosphoric acid solution, pH 3.0-acetonitrile (60 + 40, v/v), pumped at a constant flow rate of 1.0 mL/min. Measurements were made at a wavelength of 232 nm. The calibration curves were linear over the range of 10-30 microg/mL (r2 = 0.9999). The relative standard deviation (RSD) values for intraday precision were 0.94 and 1.43% for tablets and compounded capsules, respectively. The RSD values for interday precision were 0.13 and 0.82% for tablets and compounded capsules, respectively. Recoveries ranged from 97.7 to 101.8% for tablets and from 98.4 to 102% for compounded capsules. No interferences from the excipients were observed. Because of its simplicity and accuracy, the method is suitable for routine quality-control analysis for cetirizine in tablets and compounded capsules.