Dissolution Enhancement and Characterization of Nimodipine Solid Dispersions with Poloxamer 407 or PEG 6000

The solid dispersion approach is an alternative to increase drug solubility. Many carriers have been studied, but there is few information about poloxamer 407 (P407). Consequently, the objective of this study was to evaluate P407 as a carrier for nimodipine solid dispersions and to compare its solubility and dissolution rates with those from polyethylene glycol (PEG 6000). The solid dispersions were prepared by the hot melting and solvent methods and they were characterized by FTIR, DSC, solubility, and dissolution tests. The results indicated a three-fold increase in solid dispersions solubility in the presence with P407 than those prepared with PEG.

Physicochemical and dissolution profile characterization of pellets containing different binders obtained by the extrusion-spheronization process

With the purpose of evaluating the behavior of different polymers employed as binders in small-diameter pellets for oral administration, we prepared formulations containing paracetamol and one of the following polymers: PVP, PEG 1500, hydroxypropylmethylcellulose and methylcellulose, and we evaluated their different binding properties. The pellets were obtained by the extrusion/spheronization process and were subsequently subjected to fluid bed drying. In order to assess drug delivery, the United States Pharmacopeia (USP) apparatus 3 (Bio-Dis) was employed, in conjunction with the method described by the same pharmacopeia for the dissolution of paracetamol tablets (apparatus 1). The pellets were also evaluated for granulometry, friability, true density and drug content. The results indicate that the different binders used are capable of affecting production in different ways, and some of the physicochemical characteristics of the pellets, as well as the dissolution test, revealed that the formulations acted like immediate-release products. The pellets obtained presented favorable release characteristics for orally disintegrating tablets. USP apparatus 3 seems to be more adequate for discriminating among formulations than the basket method.

Metronidazole Immediate Release Formulations: A Fasting Randomized Open-Label Crossover Bioequivalence Study in Healthy Volunteers

Metronidazole is a BCS (Biopharmaceutics Classification System) class 1 drug, traditionally considered the choice drug in the infections treatment caused by protozoa and anaerobic microorganisms. This study aimed to evaluate bioequivalence between 2 different marketed 250 mg metronidazole immediate release tablets. A randomized, open-label, 2 x 2 crossover study was performed in healthy Brazilian volunteers under fasting conditions with a 7-day washout period. The formulations were administered as single oral dose and blood was sampled over 48 h. Metronidazole plasma concentrations were determined by a liquid chromatography mass spectrometry (LC-MS/MS) method. The plasma concentration vs. time profile was generated for each volunteer and the pharmacokinetic parameters C-max, T-max, AUC(0-t), AUC(0-infinity), k(e), and t(1/2) were calculated using a noncompartmental model. Bioequivalence between pharmaceutical formulations was determined by calculating 90% CIs (Confidence Intervall) for the ratios of C-max, AUC(0-t), and AUC(0-infinity) values for test and reference using log-transformed data. 22 healthy volunteers (11 men, 11 women; mean (SD) age, 28 (6.5) years [range, 21-45 years]; mean (SD) weight, 66 (9.3) kg [range, 51-81 kg]; mean (SD) height, 169 (6.5) cm [range, 156-186 cm]) were enrolled in and completed the study. The 90% CIs for C-max (0.92-1.06), AUC(0-t) (0.97-1.02), and AUC(0-infinity) (0.97-1.03) values for the test and reference products fitted in the interval of 0.80-1.25 proposed by most regulatory agencies, including the Brazilian agency ANVISA. No clinically significant adverse effects were reported. After pharmacokinetics analysis, it concluded that test 250 mg metronidazole formulation is bioequivalent to the reference product according to the Brazilian agency requirements.

Biowaiver monographs for immediate-release solid oral dosage forms: Stavudine

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing stavudine (d4T) are reviewed. According to Biopharmaceutics Classification System (BCS), d4T can be assigned to BCS class I. No problems with BE of IR d4T formulations containing different excipients and produced by different manufacturing methods have been reported and, hence, the risk of bioinequivalence caused by these factors appears to be low. Furthermore, d4T has a wide therapeutic index. It is concluded that a biowaiver is appropriate for IR solid oral dosage forms containing d4T as the single active pharmaceutical ingredient (API) provided that (a) the test product contains only excipients present in the IR d4T drug products that have been approved in a number of countries for the same dosage form, and (b) both test product and its comparator are either very rapidly dissolving or rapidly dissolving with similarity of dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8. (c) 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:1016, 2012

Microencapsulation of Ketoprofen in Blends of Acrylic Resins by Spray Drying

Microparticles of ketoprofen entrapped in blends of acrylic resins (Eudragit RL 30D and RS 30D) were successfully produced by spray drying. The effects of the proportion ketoprofen : polymer (1: 1 and 1: 3) and of spray-drying parameters (drying gas inlet temperatures of 80 and 100 degrees C; microencapsulating composition feed flow rates of 4 and 6 g/min) on the microparticles properties (drug content, encapsulation efficiency, mean particle size, moisture content, and dissolution behavior) were evaluated. Differential scanning calorimetry (DSC) thermograms and X-ray diffractograms of the spray-dried product, the free drug, and the physical mixture between the free drug and spray-dried composition (blank) were carried out. Microparticles obtained at inlet temperature of 80 degrees C, feed flow rate of 4 g/min, and ketoprofen : acrylic resin ratio of 1: 3 presented an encapsulation efficiency of 88.1%, moisture content of 5.8%, production yield around 50%, and a higher reduction in dissolution rate of the entrapped ketoprofen. Sigmoidal shape dissolution profiles were presented by the spray-dried microparticles. The dissolution profiles were relatively well described by the Weibull model, a showing high coefficient of determination, R-2, and a mean absolute error between experimental and estimated values of between 4.6 and 10.1%.

Solid Dispersion of Ursolic Acid in Gelucire 50/13: a Strategy to Enhance Drug Release and Trypanocidal Activity

Solid dispersions (SDs) are an approach to increasing the water solubility and bioavailability of lipophilic drugs such as ursolic acid (UA), a triterpenoid with trypanocidal activity. In this work, Gelucire 50/13, a surfactant compound with permeability-enhancing properties, and silicon dioxide, a drying adjuvant, were employed to produce SDs with UA. SDs and physical mixtures (PMs) in different drug/carrier ratios were characterized and compared using differential scanning calorimetry, hot stage microscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), particle size, water solubility values, and dissolution profiles. Moreover, LLC-MK2 fibroblast cytotoxicity and trypanocidal activity evaluation were performed to determine the potential of SD as a strategy to improve UA efficacy against Chagas disease. The results demonstrated the conversion of UA from the crystalline to the amorphous state through XRD. FTIR experiments provided evidence of intermolecular interactions among the drug and carriers through carbonyl peak broadening in the SDs. These findings helped explain the enhancement of water solubility from 75.98 mu g/mL in PMs to 293.43 mu g/mL in SDs and the faster drug release into aqueous media compared with pure UA or PMs, which was maintained after 6 months at room temperature. Importantly, improved SD dissolution was accompanied by higher UA activity against trypomastigote forms of Trypanosoma cruzi, but not against mammalian fibroblasts, enhancing the potential of UA for Chagas disease treatment.

An electrochemical gas sensor based on paper supported room temperature ionic liquids

A sensitive and fast-responding membrane-free amperometric gas sensor is described, consisting of a small filter paper foil soaked with a room temperature ionic liquid (RTIL), upon which three electrodes are screen printed with carbon ink, using a suitable mask. It takes advantage of the high electrical conductivity and negligible vapour pressure of RTILs as well as their easy immobilization into a porous and inexpensive supporting material such as paper. Moreover, thanks to a careful control of the preparation procedure, a very close contact between the RTIL and electrode material can be achieved so as to allow gaseous analytes to undergo charge transfer just as soon as they reach the three-phase sites where the electrode material, paper supported RTIL and gas phase meet. Thus, the adverse effect on recorded currents of slow steps such as analyte diffusion and dissolution in a solvent is avoided. To evaluate the performance of this device, it was used as a wall-jet amperometric detector for flow injection analysis of 1-butanethiol vapours, adopted as the model gaseous analyte, present in headspace samples in equilibrium with aqueous solutions at controlled concentrations. With this purpose, the RTIL soaked paper electrochemical detector (RTIL-PED) was assembled by using 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl) imide as the wicking RTIL and printing the working electrode with carbon ink doped with cobalt(II) phthalocyanine, to profit from its ability to electrocatalyze thiol oxidation. The results obtained were quite satisfactory (detection limit: 0.5 mu M; dynamic range: 2-200 mu M, both referring to solution concentrations; correlation coefficient: 0.998; repeatability: +/- 7% RSD; long-term stability: 9%), thus suggesting the possible use of this device for manifold applications.