Development and validation of an intrinsic dissolution method for nimodipine polymorphs

The polymorphs of nimodipine, Modification I (Mod I), the metastable racemate, and Modification II (Mod II), the stable conglomerate, were evaluated by means of the intrinsic dissolution procedure. For this purpose, a hydro alcoholic solution (ethanol:water, 50:50, v/v) was selected as the dissolution medium, maintained at 37±0.5°C. Different rotation speeds were tested (50, 75 and 100 rpm) and the lower one was chosen for the test validation. Although the sample initially characterized as polymorph Mod I presented higher intrinsic dissolution rates in all the conditions tested, no statistical differences were noticed between the two polymorphs. This result can be attributed to the partial solution-mediated phase transformation from Mod I to Mod II, detected through X-ray powder diffraction and differential scanning calorimetry. Also, reliable intrinsic dissolution rate data were acquired for the polymorph Mod II. The dissolution method was validated, being considered stable, specific, linear, sensible, accurate and precise.      

Pharmaceutical approaches involving carvedilol characterization,compatibility with different excipients and kinetic studies

This study was performed to investigate the physical–chemical characteristics of carvedilol (CRV), complemented by compatibility studies with a great variety of pharmaceutical excipients. Thermogravimetry and differential scanning calorimetry, supported by diffuse reflectance infrared fourier transform spectroscopy (DRIFT), X-ray powder diffraction, and scanning electron microscopy (SEM) were selected as the solid-state techniques for the intended analyses. In addition, non-isothermal methods were employed to investigate kinetic data of CRV decomposition process under nitrogen and air atmospheres. CRV is characterized by an endothermic sharp event (T _peak = 389.81 K and ΔH _fusion of ?176.28 J g^?1) and a thermal decomposition behavior in two stages, totalizing 98 % of mass loss. The CRV pattern diffraction presents prominent peaks at 2θ: 5.92°, 14.90°, 18.62°, 24.47°, and 26.30°, and the DRIFT spectrum showed the main characteristics bands for CRV chemical functional groups. The SEM photomicrographs demonstrate that CRV is characterized by irregular blocky shaped crystals. Zero order kinetics was determined by Ozawa method in both nitrogen and air atmospheres. The compatibility results showed no evidence of any incompatibility among CRV and all the excipients analyzed.     

Sibutramine hydrochloride monohydrate

In the present work, the thermal decomposition of sibutramine hydrochloride monohydrate (SBT) (an appetite suppressant agent) was studied using differential scanning calorimetry (DSC) and thermogravimetry/derivative thermogravimetry (TG/DTG). Solid-state characterization was carried out by diffuse reflectance infrared fourier transform spectroscopy (DRIFT), scanning electron microscopy (SEM) and X-ray powder diffraction (XRPD). Isothermal and non-isothermal methods were employed to determine the kinetic data of decomposition process. From isothermal experiments, activation energy (Ea) can be obtained from slope of ln t versus 1/T, and the value obtained was 96.06 and 101.43 kJ mol⁻¹ in N₂ and air atmospheres, respectively. For non-isothermal method Ea can be obtained from plot of logarithms of heating rates, as a function of inverse of temperature, resulting in a value of 96.56 and 98.22 kJ mol⁻¹ in N₂ and air atmospheres, respectively. The compatibilities of several commonly used pharmaceutical excipients (microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide, lactose monohydrate) and empty hard-gelatin capsules with SBT were evaluated using DSC. The 1:1 physical mixtures of these excipients with SBT showed physical interaction of the drug with magnesium stearate. On the other hand, DRIFT results did not evidence any chemical modifications.     

High-performance column liquid chromatographic method for the simultaneous determination of buclizine, tryptophan, pyridoxine, and cyanocobalamin in tablets and oral suspension

An HPLC method was developed and validated for the simultaneous determination of buclizine, tryptophan, pyridoxine, and cyanocobalamin in pharmaceutical formulations. The chromatographic separation was carried out on an RP-C18 column using a mobile phase gradient of methanol, 0.015 M phosphate buffer (pH 3.0), and 0.03 M phosphoric acid at a flow rate of 1.0 mL/min and UV detection at 230, 280, and 360 nm, respectively, for buclizine, tryptophan, pyridoxine, and cyanocobalamin. The method validation yielded good results with respect to linearity (r>0.999), specificity, precision, accuracy, and robustness. The RSD values for intraday and interday precision were below 1.82 and 0.63%, respectively, and recoveries ranged from 98.11 to 101.95%. The method was successfully applied for the QC analysis of buclizine, tryptophan, pyridoxine, and cyanocobalamin in tablets and oral suspension.     

Development and Validation of Stability Indicating LC Method to Quantify Captopril in Tablets of Controlled Release

An accurate, simple, reproducible, and sensitive liquid chromatographic method was developed and validated for the captopril determination in controlled release tablets. The analyses were performed at room temperature on a reversed-phase Phenomenex Luna C₁₈ column (250 mm × 4.6 mm). The mobile phase was composed of water:methanol (45:55; v/v) pH 2.5, and it was eluted isocratically at a 1.0 mL min⁻¹ flow rate. The method was validated in terms of specificity, linearity, quantification limit, detection limit, accuracy, precision and robustness. The response was linear in the range 0.3–1.5 mg mL⁻¹ (r ² = 0.9983). The relative standard deviation values for inter-and intra-day precision were 0.77% and 0.50%, respectively. Recoveries ranged between 97.7 and 99.1%. The method was successfully applied for the determination of captopril in the developed formulations.

     

Thermal decomposition kinetics and compatibility studies of primaquine under isothermal and non-isothermal conditions

Primaquine (PQ) is the drug of choice for the radical cure of Plasmodium vivax malaria, and currently being administered in solid dosage form. In this study, the compatibility studies were carried out using differential scanning calorimetry (DSC), thermogravimetry (TG), and fourier transformed infrared (FT-IR). Non-isothermal and isothermal methods were employed to investigate kinetic parameters under nitrogen and air atmospheres using TG. The DSC investigations obtained by physical mixtures showed slight alterations in the melting temperatures of PQ with some excipients. The FT-IR confirmed the possible interactions obtained by DSC for the physical mixtures with PQ and lactose, magnesium stearate and mannitol. The results showed that the thermal decomposition followed a zero order kinetic in both atmospheres in non-isothermal method. The activation energy in both methods using nitrogen atmosphere was similar, and in air atmosphere the activation energy decreased.     

Development and Validation of Stability Indicating LC Method to Quantify Captopril in Tablets of Controlled Release

An accurate, simple, reproducible, and sensitive liquid chromatographic method was developed and validated for the captopril determination in controlled release tablets. The analyses were performed at room temperature on a reversed-phase Phenomenex Luna C₁₈ column (250 mm × 4.6 mm). The mobile phase was composed of water:methanol (45:55; v/v) pH 2.5, and it was eluted isocratically at a 1.0 mL min⁻¹ flow rate. The method was validated in terms of specificity, linearity, quantification limit, detection limit, accuracy, precision and robustness. The response was linear in the range 0.3–1.5 mg mL⁻¹ (r ²  = 0.9983). The relative standard deviation values for inter-and intra-day precision were 0.77% and 0.50%, respectively. Recoveries ranged between 97.7 and 99.1%. The method was successfully applied for the determination of captopril in the developed formulations.     

Development and Validation of a Stability-Indicating LC Method to Quantify Hydrochlorothiazide in Oral Suspension for Pediatric Use

A stability-indicating reversed-phase high-performance liquid chromatography (LC) method was developed and validated for the determination of hydrochlorothiazide in an oral suspension. Isocratic chromatography was performed on a C₁₈ column with 0.1 M sodium phosphate buffer pH 3.0/acetonitrile (70:30 v/v) as mobile phase, at a flow rate of 1.3 mL min⁻¹, and UV detection at 254 nm. The method was linear (r ² = 0.9998), accurate (mean recovery = 100.3%), and precise (RSD <2%). It was also validated for specificity and robustness. The method was successfully applied for the quality control analysis of a new pharmaceutical formulation of HCTZ for pediatric use.     

Development and validation of an RP-HPLC method to quantitate acyclovir in cross-linked chitosan microspheres produced by spray drying

An accurate, simple, reproducible, and sensitive liquid chromatographic method is developed and validated to quantitate acyclovir (ACV) in cross-linked chitosan microspheres produced by spray drying. The analysis is carried out using a reversed-phase C18 column with UV-vis detection at 254 nm. The mobile phase is diluted with pure water and acetonitrile (95:5 v/v) at a flow-rate of 0.8 mL/min. The parameters used in the validation process are: linearity, range, quantitation limit, detection limit, accuracy, specificity precision, and ruggedness. The retention time of acyclovir is approximately 3.5 min with symmetrical peaks. The linearity in the range of 1-10 microg/mL presents a correlation coefficient of 0.9999. The chitosan and the tripolyphosphate in the formulation do not interfere with the analysis, and the recovery is quantitative. Results are satisfactory, and the method proves to be suitable to quantitate ACV in cross-linked chitosan microspheres.     

Compatibility studies between captopril and pharmaceutical excipients used in tablets formulations

Captopril (CAP) was the first commercially available angiotensine-converting enzyme (ACE) inhibitor. In the anti-hypertensive therapy is considered the selected drug has to be therapeutically effective together with reduced toxicity. CAP is an antihypertensive drug currently being administered in tablet form. In order to investigate the possible interactions between CAP and excipients in tablets formulations, differential scanning calorimetry (DSC) and thermogravimetric (TG) analysis completed by X-ray powder diffraction (XRPD) and Fourier transform infrared spectroscopy (FTIR) were used for compatibility studies. A possible drug-excipient interaction was observed with magnesium stearate by DSC technique.