Paloma Frutos

Gentamicin release from modified acrylic bone cements with lactose and hydroxypropylmethylcellulose.

Modified polymethylmethacrylate (PMMA) bone cements formulations were prepared by including different proportions of gentamicin and release modulators such as lactose or hydroxypropylmethylcellulose (HPMC). Surface aspect, gentamicin release and porosity of these modified formulations were studied by means of scanning electron microscopy (SEM), a specially designed system for the dissolution studies of the bone cements, and mercury intrusion porosimetry. Lactose modified cements presented an irregular surface with numerous hollows and voids due to the lactose dissolution. HPMC cements presented a characteristic laminated and flaky surface. The drug release of lactose formulations was up to four-fold greater (13%) than the commercial bone cement CMW1 Gentamicin one (3%). The amount of gentamicin eluted at the first withdrawn sample ranged from 30% to 60% of total gentamicin released over the assay. Gentamicin release from lactose formulations increased as lactose percentage was increased which agree with the porosity results. Nevertheless, the use of release modulator HPMC increased porosity, but did not produce an increase in the gentamicin release. HPMC dissolution creates a surrounding sticky and viscous medium similar to a gel that makes the gentamicin release from the cement matrix difficult.

Analysis of diclofenac sodium and derivatives.

There are two reasons explaining why several researchers have carried out the in vitro release studies of diclofenac sodium (DFNa) using pH media of above 6.5. Firstly the pH dependence of solubility, and secondly the intramolecular cyclization suffered under acidic conditions which causes the salt to become inactivated. Nevertheless, many commercially available pharmaceutical dosage forms have no protective coat to avoid the inactivation in the gastric juices. A possible explanation may be found if reconstitution of the cyclated form takes place. It is therefore necessary to study the behaviour of diclofenac sodium when it is submitted to the action of different solutions in a wide pH range. To perform this study five analytical methods have been employed: UV-vis spectrophotometry, differential scanning calorimetry (DSC), infrared analysis (IR), X-ray diffractometry (DRX) and energy dispersive X-ray analysis (EDS).

Release of gentamicin sulphate from a modified commercial bone cement. Effect of (2-hydroxyethyl methacrylate) comonomer and poly(N-vinyl-2-pyrrolidone) additive on release mechanism and kinetics

The influence of the (2-hydroxyethyl methacrylate) (HEMA) monomer addition as a comonomer to the cement liquid component and of a polymer, poly(N-vinyl-2-pyrrolidone) (PVP) to the solid component of a standard CMW-1 bone cement on gentamicin sulphate (GS) on its drug release properties have been studied. The addition of HEMA modifies the habit of the delivery curves. The incorporation of PVP into the cement matrix, apparently, did not very much modify the shape of the HEMA modified cement release curves, but led to a remarkable increase of the maximum amount of GS released. This effect was proportional to the PVP concentration incorporated. From the matrix composition and SEM data, a model based on the morphology of the matrix has been proposed. The cumulative amount of GS released by each slab Mt is most adequately fitted and represented by the equation Mt = c + at 1/2 + b[1 - exp(-nt)], which corroborates that the release occurs according to the model proposed. by means of three discrete mechanisms, namely: (i) a short-term initial elution due to the imperfections in the poly(methyl methacrylate) covering of the most external GS beads, burst effect by the buffer solution; (ii) followed by a fracture by stress cracking in an active media of the coated GS beads located on the external surface of the matrix where water molecules enter to dissolve GS molecules releasing them into the buffer solution by a diffusion-controlled process; and (iii) a third process in which the buffer solution penetrates into the internal voids and cracks creating a series of channels in a labyrinthic structure, which may facilitate the access of water molecules to the plastic-coated GS beads within the bulk matrix. This third process is enhanced by the incorporation of PVP beads as dissolved molecules within the matrix. This water-soluble additive is leachable, generating a highly porous structure in the cement. This HEMA and PVP modified cement may be used as a drug delivery system to modulate the GS release rate.

Lyophilized Lecithin Based Oil-Water Microemulsions as a New and Low Toxic Delivery System for Amphotericin B

AbstractPurpose. To develop and investigate lecithin based oil-water microemulsions as potential amphotericin B (AmB) delivery systems and to evaluate their in vivo acute toxicity. Methods. AmB was added to the microemulsion and its location was evaluated by partitioning studies and UV-visible spectrophotometric analysis of the drug. Both, non-lyophilized and reconstituted microemulsions were characterised and assessed for their stability. Single-dose acute toxicity of the AmB microemulsion was studied on male albino Webster-derived CD-1 mice and compared with Fungizone®. Results. The studies performed showed that AmB was intercalated on the oil-water interface of the microemulsion as a complex formed with lecithin molecules. AmB addition did not seem to modify the rheological properties of the original system, but had an effect on its particle size distribution. Lyophilization of the microemulsion led to an oily cake, easily reconstituted and stable at the conditions studied. Single-dose acute toxicity studies proved that the LD50 of AmB microemulsions was of 4 mg kg−1 of animal weight, compared with 1 mg kg−1 found for Fungizone®. Conclusions. Lyophilized lecithin based oil-water microemulsions appear to be valuable systems for the delivery of AmB in terms of easy and low-cost manufacturing, stability and safety compared with the formulations already in market.

A validated quantitative colorimetric assay for gentamicin

A colorimetric procedure was developed for the quantification of gentamicin. The method was based on the ninhydrin reaction with primary and secondary amines present in the gentamicin. This reaction produces a purple colour. The effects of several factors including pH, ninhydrin concentration and reaction time were investigated to optimize the assay method. Using the assay protocol, the absorption of the gentamicin-ninhydrin mixtures at 400 nm had a linear relationship with the gentamicin concentration ranging from 30 to 120 microg/ml. The colorimetric gentamicin assay reported herein is of great practical value because it is reproducible, sensitive, simple and extremely inexpensive.

The influence of the copolymer composition on the diltiazem hydrochloride release from a series of pH-sensitive poly[(N-isopropylacrylamide)-co-(methacrylic acid)] hydrogels.

A series of poly[(N-isopropylacrylamide)-co-(methacrylic acid)] (P[(N-iPAAm)-co-(MAA)]) hydrogels was investigated to determine the composition that exhibits a better pH-modulated release of diltiazem hydrochloride (DIL.HCl). For this purpose hydrogel slabs were loaded with DIL.HCl by the immersion method, and its release under acidic medium (0.1N HCl, pH 1.2) and in phosphate buffer pH 7.2, using United States Pharmacopeia (USP) 24 Apparatus 1, was investigated. According to the results from the slabs, copolymers with 85% mol N-iPAAm content were selected to prepare tablets with different particle size. The effect of pH and particle size changes on DIL.HCl release from these last hydrogel tablets was investigated by a stepwise pH variation of the dissolution medium. The amount of DIL.HCl released from high N-iPAAm content copolymer slabs under acidic pH medium was not only very low but it was also released at a slow rate. In the 85% N-iPAAm tablets, significant differences between and within release profiles were found as a function of particle size and pH, respectively. A relationship between particle size and release rate has been found. The lower DIL.HCl release at acidic pH from enriched N-iPAAm copolymers is interpreted by a cooperative thermal- and pH-collapse. Although for the whole range of copolymer composition a dependence of the equilibrium of swelling on the pH was found, DIL.HCl release experiments indicated that hydrogels with 85% mol N-iPAAm are the more adequate to be used for modulated drug delivery systems. Additionally, the particle size of the tablet can be used to tailor the release rate.

Extraction and liquid-chromatographic determination of amphotericin B in oil-water lecithin-based microemulsions

SummaryA method employing extraction then reproducible reversed-phase high-performance liquid chromatography (RPHPLC) with monitoring of the drug by absorbance at 405 nm has been developed and validated for the determination of amphotericin B in oil-water lecithin-based microemulsions. The precision and accuracy of the method are excellent (SD 2.4% and 4.2%, respectively). The established linearity range was 10–60 μg mL−1 (r2=0.9967). The recovery of amphotericin B from spiked placebo was >90% over the linear range. The extraction procedure was simple and the HPLC conditions were able to separate the drug from its degradation products and excipients. The method has been used successfully for determining the amphotericin B content of microemulsions and for evaluating the chemical stability of amphotericin B-loaded microemulsions.

Diclofenac Sodium Microcapsules: In Vitro Testing Considerations

AbstractDespite the great proliferation of microcapsules in the pharmaceutical field, there are no official guidelines for “in vitro” testing. This lack of official information means that many devices and processes have to be used to determine accurately the dissolution characteristics of microcapsules. Our objective is to review the “in vitro” dissolution tests performed by researchers and to establish the best conditions to test diclofenac sodium microcapsules obtained by using a polymeric solvent extraction method, with three different in vitro systems. Some mathematical adjustments have been made with the results, in order to establish the most appropriate in vitro dissolution system.

Matrix Tablets Containing HPMC and Polyamide 12: Comparison of Dissolution Data Using the Gompertz Function

There have been several studies reported which have evaluated the controlled drug release from hydrophillic (1,2) or hydrophobic (3) polymeric matrix tablets, but the Y do not show anything about mixed matrices containing the two kinds of polymeric materials. In a previous paper, we have studied the in vitro dissolution data from mixed matrix tablets containing HPMC and polyamide 12, by means of an analysis of variance of parameters which do not require any model hypothesis. Now the effect on the dissolution profiles of different ratios of the hydrophillic polymer and the hydrophobic one, is evaluated by a mathematical model

Comparison of UV spectrophotometric and LC methods for the determination of nortriptyline hydrochloride in polysorbate 80 based oil/water (o/w) microemulsions

A new rapid, reliable and specific UV spectrophotometric method was developed for the determination of nortriptyline hydrochloride formulated into o/w microemulsions. The UV spectra of nortriptyline standard solution in methanol and placebo (microemulsion without nortriptyline) were recorded over the wavelength range 200-600 nm and the spectra for placebo and nortriptyline loaded microemulsion were recorded over the range 260-400 nm in order to determine the overlapping that might appears, and hence to set the wavelength that could be used for the quantitative analysis. This method was validated and compared with a liquid chromatography (LC) procedure used for the quantitative analysis of the drug. Both methods showed excellent precision and accuracy with RSD values of 2.37 and 1.41%, respectively, for the LC method, and values of 1.24 and 2.88%, respectively, for the UV spectrophotometric method. The established linearity range was 10-50 microg ml(-1) (r2 = 0.9985) and 20-60 microg ml(-1) (r2 = 0.9979) for the HPLC and UV spectrophotometric methods respectively. The recoveries of nortriptyline from spiked placebos were > 95% for both methods over the linear range. The methods have been successfully used for determining the nortriptyline content of microemulsions and for evaluating the chemical stability of the drug in nortriptyline-loaded microemulsions.