Excipients

The aim of this study was to evaluate the effects of preparation method and the type of surfactant on the properties of cephalexin (CPX) microspheres in order to obtain delivery systems suitable for the treatment of dairy mastitis. Microspheres were obtained using various preparation conditions and their physicochemical characteristics such as size, loading efficiency, morphology, and drug crystallinity were investigated. Antibacterial activity of microspheres from the optimum preparation condition was also studied. CPX microspheres were prepared by two different W/O/W emulsion solvent evaporation methods using PLGA as a matrix forming polymer. Several types of surfactants including nonionic, cationic, and anionic at different concentrations were used for preparation of the particles. The type and concentration of surfactant did neither affect the size nor morphology of the microspheres but showed a pronounced effect on the CPX encapsulation efficiency. It was found that Tween 80 showed the highest drug encapsulation efficiency (66.5%). Results from X-ray diffraction diffractograms and differential scanning calorimetry thermograms indicated that CPX entrapped in these microparticles was amorphous. Assessment of antibacterial activity showed that the obtained CPX microspheres exhibited good inhibition with minimum inhibitory concentration and minimum bactericidal concentration values of 128 µg/mL and 2,048 mg/mL against Staphylococcus aureus ATCC 25923, 512 µg/mL and 4,096 mg/mL against Escherichia coli ATCC 25922, respectively.

Solid-liquid equilibrium (SLE) for binary mixture of Propafenone Hydrocloride (PP) with Metoprolol Tartrate (MT) was investigated using differential scanning calorimetry (DSC) and corresponding activity coefficients were calculated. Simple eutectic behavior for this system was observed. The excess thermodynamic functions: G(E) and S(E) for the pre-, post-, and eutectic composition have been obtained using the computed activity coefficients data of the eutectic phase with their excess chemical potentials μi(E) (i=1, 2). The experimental solid-liquid phase temperatures were compared with predictions obtained from available eutectic equilibrium models. The results indicate non-ideality in this mixture. Also, the compatibility of each component and their eutectic mixture with usual excipients was investigated, and the DSC experiments indicate possible weak interactions with α-lactose monohydrate and compatibility with corn starch. The results obtained were confirmed by FT-IR measurements.

This investigation evaluated some new (Preflo) and existing commercially available (Starch 1500, Star Tab) modified starches as direct compression excipients. Preflo corn starches (CH-10, CH-20, CH-30) and Preflo potato starches (P-250, PI-10, PJ-20) were evaluated and compared with respect to their pharmaceutical properties such as particle size, density, flowability, friability, and compression properties. Preflo starches showed a high bulk density and good flowability. Preflo corn starches and Star Tab formed harder tablets than Preflo potato starches and Starch 1500. Data from the Athy-Heckel plots indicated that the Preflo starches are soft materials and, unlike Starch 1500, undergo plastic deformation. Tablets containing acetaminophen were also compressed with the starches and disintegration and dissolution studies were conducted. Starch 1500 tablets disintegrated in 3.5 min, whereas none of the Preflo starch tablets disintegrated in 30 min. While complete acetaminophen releas...

Solubilization of hydrophobic drugs at the molecular level as inclusion complexes inside cyclodextrins (CDs) offers a good alternative for improving their stability, solubility and bioavailability, and for preventing against their possible toxicity or controlling secondary effects. Therefore CDs are widely used as solubilizing excipients. However since dissociation takes place too readily upon dilution, inclusion complexes inside simple water-soluble CD appears ineffective for drug delivery applications. Chemical modifications of CDs allow them to self-organize as larger assemblies useful for resolving this lability issue. Depending on the position, the number and the nature of these groups, amphiphilic CDs can form assemblies such as vesicles, solid-lipid nanoparticles, nanospheres, liquid crystals, or micellar systems. This review deals with the synthesis of amphiphilic cyclodextrins leading to supramolecular assemblies and the physical properties of these assemblies. From the fir...

Disintegration performance was measured by analysing both water ingress and tablet swelling of pure microcrystalline cellulose (MCC) and in mixture with croscarmellose sodium using terahertz pulsed imaging (TPI). Tablets made from pure MCC with porosities of 10% and 15% showed similar swelling and transport kinetics: within the first 15 s, tablets had swollen by up to 33% of their original thickness and water had fully penetrated the tablet following Darcy flow kinetics. In contrast, MCC tablets with a porosity of 5% exhibited much slower transport kinetics, with swelling to only 17% of their original thickness and full water penetration reached after 100 s, dominated by case II transport kinetics. The effect of adding superdisintegrant to the formulation and varying the temperature of the dissolution medium between 20°C and 37°C on the swelling and transport process was quantified. We have demonstrated that TPI can be used to non-invasively analyse the complex disintegration kineti...

It has been observed previously that xanthan gum (XG) and hydroxypropylmethyl cellulose (HPMC) show different drug release behavior. In order to clarify these findings, the rheological properties of both polymers have been determined by oscillatory as well as by steady shear measurements. Aqueous solutions of 4 and 7% (w/w) polymer have been used to simulate the outer surface of a hydrated tablet. The dynamic moduli, i.e., storage modulus (G′) and loss modulus (G″) of the two polymers have been determined in pure water and USP phosphate buffer pH 7.4 at different dilutions. In this concentration range XG solution exhibits “gel-like” behavior, while HPMC behaves as a typical polymer solution. These findings are quite consistent with the reported higher ability of XG matrices to retard drug release than HPMC matrices for controlled-release formulation. The effects of differences in drug solubility and acidity, as well as the addition of lactose, and of the ionic strength of the medium on the rheological properties of XG and HPMC solutions have been studied in detail. Among these parameters, only the salt concentration exerts an enhancing effect on both moduli of XG, while no detectable influence on HPMC solution could be observed.

The objective of the present study was to develop a once-daily sustained-release (SR) matrix tablet of famotidine. Nine different formulations (F1–F9) were prepared by direct compression method using Avicel PH101 as filler/binder in the range of 41–27% in F1–F3, 18–22% in F4–F7, and 16–18% in F8–F9 and hydroxypropyl methylcellulose (4,000 cps) as hydrophilic matrix was used in F1–F3 from 19% to 30%, around 40% in F4–F7, and 42–45% in F8–F9. Talc and Aerosil were added in the ratio of 0.7–1.2%. The tablets were subjected to various physical parameters including weight variation test, hardness, thickness, diameter, friability, and in vitro release studies. Assay was also performed according to the USP 30 NF 25 procedure. The results of the physical parameters and assay were found to be within the acceptable range. In vitro dissolution results indicated that formulation F4–F7, having around 40% of rate control polymer, produced a SR pattern throughout 24 h. F1–F3 showed drug release at a faster rate, while F8–F9 released much slower, i.e., r 2 = 0.984) and F6 in Korsmeyer and Higuchi (r 2 = 0.992 and 0.988). The parameter n indicated anomalous diffusion, while β in Weibull showed a parabolic curve with higher initial slope. The f 2 similarity test was performed taking F4 as a reference formulation. Only the F5–F7 formulations were similar to the reference formulation F4. The mean dissolution time was around 10 h for the successful formulation.

An HPLC method to determine simultaneously ketoconazole and formaldehyde in an anti-dandruff shampoo, originally developed on a long column, was transferred to two short columns with similar stationary phase properties, but with a length of at the most 30% of the initial one. Using the conventional column as reference, the fast HPLC methods on the short columns were validated. The validation characteristics consisted of selectivity, linearity range, precision (repeatability and time-different intermediate precision), bias and robustness. For the ketoconazole assay, linearity for peak area was found in the concentration range up to 0.20 mg/ml. For formaldehyde, two calibration ranges (0-10 x 10(-5) and 0-10 x 10(-4)%) were linear, both for peak area and height. The assays for both ketoconazole and formaldehyde in these ranges showed no bias and an acceptable precision, although the precision found with the short columns was slightly worse than with the long one. The robustness tests ...

In the present study, viscous solutions of cysteamine hydrochloride (CH) were prepared by using 0.5%, 1.0%, 1.5% or 3.0% of hydroxypropylmethylcellulose (HPMC) and were evaluated for their in-vitro characteristics and stability. Osmolalities, pH and viscosity of the formulations were determined. The influence of benzalkonium chloride and autoclave sterilization on solution characteristics was also investigated. For stability assessment, the viscous solutions were stored at +4 and +25 °C over 12 months. In-vitro characteristics and CH contents of the stored solutions were monitored. Irritation tests for the formulations were evaluated on rabbit eyes. Dialysis sac technique was used to perform in vitro release study of the solutions containing 1.0% and 1.5% HPMC. All of the viscous solutions tested showed non-newtonian (dilatant) flow behavior. Osmolality values were ranked between 351.2 ± 6.2 and 355.1 ± 7.9 mOsm kg−1, and pH values were between 3.97 ± 0.1 and 3.98 ± 0.2 for all the solutions. Furthermore, no significant changes in dilatant behavior, osmolality or pH values of the pure HPMC solutions were observed. After addition of the excipients or CH-excipients, increased viscosity values were noted in these formulations. Neither benzalkonium chloride nor autoclave sterilization had any influence on viscosity, pH or osmolality values of the solution containing 1.5% HPMC. Stability studies showed that a faster decrease in the concentration of CH was observed in the formulations stored at 25 °C compared to those kept at 4 °C; no changes were determined in osmolality values of the solutions at all storage conditions. Increased pH and decreased viscosity values were noted in HPMC solutions containing CH and excipients, while no changes in these values were observed for pure HPMC solutions kept at 4 and 25 °C. In vitro release tests revealed that 81.2% and 85.3% of CH were released from the viscous solutions containing 1.5% and 1% HPMC, respectively, in 8 h. No irritation was observed when the viscous solutions were tested on rabbit and human eyes.

The objective of the study was to formulate and evaluate controlled release polymeric tablets of Diclofenac Potassium for the release rate, release patterns and the mechanism involved in the release process of the drug. Formulations with different types and grades of Ethyl Cellulose Ether derivatives in several drug-to-polymer ratios (D:P) were compressed into tablets using the direct compression method. In vitro drug release studies were performed in phosphate buffer (pH 7.4) as dissolution medium by using USP Method-1 (Rotating Basket Method). Similarity factor f2 and dissimilarity factor f1 were applied for checking the similarities and dissimilarities of the release profiles of different formulations. For the determination of the release mechanism and drug release kinetics various mathematical/kinetic models were employed. It was found that all of the Ethocel polymers could significantly slow down the drug release rate with Ethocel FP polymers being the most efficient, especiall...

The aim of the present paper was to investigate the influence of different formulation parameters on the rheological and functional properties of emulgels (gelified emulsions), intended for the buccal administration of the antiinflammatory drug flurbiprofen. The influence of formulation parameters, such as (a) the amount of gelling polymeric emulsifier (Pemulen 1621 TR-1) used, (b) the oil to water ratio present in the O/W emulgel and finally (c) the pH of the formulation, was studied by a experimental design (DoE) approach. Formulations were analyzed in term of size and morphology of the internal semi-solid oil droplets as well as in term of rheological properties in the presence or in the absence of flurbiprofen by "shear stress vs. shear rate tests" and "frequency sweep tests". Emulgels were also characterized in vitro both by bioadhesion tests and release studies. In particular release studies demonstrated that flurbiprofen is released by the emulgels in a co...

Nine formulations to be used as stick bases were manufactured using sodium stearate, propyleneglycol, and water, adding different concentrations of the following conditioning agents: octyldodecanol, PPG-5-ceteth-20, and PPG-15-stearyl ether. Free-choice-profile methodology was used to select the most adequate concentration of the agents in order to improve sensory properties. The sensory descriptors were grouped into four categories: stick aspect, sensations during application, sensations immediately after application, and sensations five minutes after application. Formulations containing 4% and 6% octyldodecanol and 2% PPG-15-stearyl ether were considered inadequate, since they showed unwanted qualities such as exudation, a slow absorption rate, high oiliness, and residue. Formulations containing 2% octyldodecanol; 2%, 4%, and 6% PPG-5-ceteth-20; and 4% and 6% PPG-15-stearyl ether presented different characteristics regarding the four categories of descriptors evaluated, all of the...

This study presents the in vitro and in vivo testing of anti-inflammatory drug containing creams, hydrogels and organogels for dermal use. In vitro penetration studies were performed with products by measuring the diffused drug amount through synthetic membranes soaked in isopropyl myristate (IPM). Our developed preparations were investigated under in vitro conditions together with two marketed medicinal products used as reference preparations. In vivo studies were carried out on anaesthetized male Wistar rats; the carrageenan-induced paw oedema decreasing effect of twelve different formulations and the reference products were measured in comparison with a control group. All - previously in vitro screened - selected products reduced paw oedema in rats. Significant differences were found among the developed products both in vitro and in vivo. Correlation between the in vitro penetration studies and in vivo results were found in the case of o/w creams, organogels and hydrogels.

This report presents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives and contaminants, with a view to recommending acceptable daily intakes for humans, and to prepare specifications for the identity and purity of food additives. The first part of the report contains a general discussion of principles governing the toxicological evaluation of food additives and contaminants, including flavouring agents, and the establishment and revision of specifications, with comments concerning limits for arsenic, lead and heavy metals. A summary follows of the Committee's evaluations of toxicological data on various specific food additives (including tert-butylhydroquinone, mineral oils, waxes and alitame) and on beta-cyclodextrin, nitrate, nitrite, potassium bromate and the contaminants ochratoxin A and patulin. Annexed to the report are a table summarizing the committee's recommendations for acceptable daily intakes of these ...