ABSTRACT
Ketotifen fumarate is a non-bronchodilator anti-asthmatic drug which inhibits the effects of certain endogenous substances known to be inflammatory mediators, and thereby exerts antiallergic activity. The present study describes the formulation of a sustained release nanoparticle [NP] drug delivery system containing ketoftifen, using poly [D,L lactide-co-glycolide] acid [PLGA]. Biodegradable NPs were prepared using 50: 50 PLGA by a water in-oil-in-water [w/o/w] double emulsion-solvent evaporation procedure and characterized for drug content, DSC [differential scanning calorimetry, XRD [X-ray diffractionl], FTIR [Fourier transform spectroscopy], particle size, surface morphology using scanning electron microscopy, and drug release rate. The effects of different drug-to-polymer ratios on the characteristics of the NPs were investigated. NPs prepared were spherical with a smooth surface. Size of NPs was dependent on the concentration of polymer [10 mg/mL, 754.6 nm]. Increasing the external organic phase volume [primary emulsion] resulted in larger particles with higher encapsulation efficiency [55%]. The best drug to polymer ratio in the NP was F[3] [1:10 ratio] which showed loading efficiency of 55%, and mean particle size of 754.6 nm, respectively. The FTIR, XRPD, and DSC results ruled out any chemical interaction between the drug and PLGA. The NPs prepared with low ratio of drug to polymer [1:5] F[1] formulation showed faster dissolution rate than those with high drug to polymer ratio [1:10] F[3] formulation. In conclusion, by selecting an appropriate level of the investigated parameters, spherical NPs with encapsulation efficiencies higher than 55% and a prolonged drug release over 24h [73.67-90.05%] were obtained
ABSTRACT
The present study involves preparation and evaluation of gastric-mucoadhesive microparticles with Metformin Hydrochloride as model drug for prolongation of gastric residence time. The microparticles were prepared by the emulsification solvent evaporation technique using polymers of Carbomer 934p [C] and Ethylcellulose [EC]. The microparticles were prepared by emulsion solvent evaporation method [O1/O2]. Disc formulations were prepared by direct compression technique from microparticles. In the current study, gastric-mucoadhesive microparticles with different polymers ratios [CP:EC] were prepared and were characterized by encapsulation efficiency, particle size, flowability, mucoadhesive property and drug release studies. The best polymers ratio was 1:3 [F2] with Carbomer 934p [as mucoadhesive polymer] and ethylcellulose [as retardant polymer], respectively. The production yield microparticles F2 showed 98.80%, mean particle size 933.25 mm and loading efficiency%98.44. The results were found that microparticle discs prepared had slower release than microparticles [p > o.o5]. The microparticles exhibited very good percentage of mucoadhesion and flowability properties. The release of drug was prolonged to 8 h [71.65-82.22%] when incorporated into mucoadhesive microparticles. The poor bioavailability of metformine is attributed to short retention of its dosage form at the absorption sites [in upper gastrointestinal tract]. The results of mucoadhesion study showed better retention of metformine microparticles [8 h] in duodenal and jejunum regions of intestine [F1, 1:2 ratio of CP:EC]. Therefore, it may be concluded that drug loaded gastric-mucoadhesive microparticles are a suitable delivery system for metformin hydrochloride, and may be used for effective management of NIDDM [Non Insulin Dependent Diabetes Mellitus]
ABSTRACT
A Box-Behnken design with three replicates was used for preparation and evaluation of Eudragit vancomycin [VCM] nanoparticles prepared by double emulsion. The purpose of this work was to optimize VCM nanoparticles to improve the physicochemical properties. Nanoparticles were formed by using W1/O/W2 double-emulsion solvent evaporation method using Eudragit RS as a retardant material. Full factorial design was employed to study the effect of independent variables, RPM [X1], amount of emulsifier [X2], stirring rate [X3], volume of organic phase [X4] and volume of aqueous phase [X5], on the dependent variables as production yield, encapsulation efficiency and particle size. The optimum condition for VCM nanoparticles preparation was 1:2 drug to polymer ratio, 0.2 [%w/w] amount of emulsifier, 25 mL [volume of organic phase], 25 mL [volume of aqueous phase], 3 min [time of stirring] and 26000 RPM. RPM and emulsifier concentrations were the effective factors on the drug loading [R2 = 90.82]. The highest entrapment efficiency was obtained when the ratio of drug to polymer was 1:3. Zeta [zeta] potential of the nanoparticles was fairly positive in molecular level. In vitro release study showed two phases: an initial burst for 0.5 h followed by a very slow release pattern during a period of 24 h. The release of VCM was influenced by the drug to polymer ratio and particle size and was found to be diffusion controlled. The best-fit release kinetic was achieved with Peppas model. In conclusion, the VCM nanoparticle preparations showed optimize formulation, which can be useful for oral administrations
Subject(s)
Acrylic Resins , Nanoparticles , Drug CompoundingABSTRACT
Theophylline, a xanthenes derivative, is still widely used as an effective bronchodilator in the management of asthmatic patients. It is used both as a prophylactic drug and to prevent acute exacerbations of asthma. The aim of study was to formulate and evaluate effect of the microencapsulation of theophylline loaded nanoparticles on the reduction of burst release. Microparticles [simple and composite] and nanoparticles were prepared by using water-in-oil-in-water [W[1]/O/W[2] double-emulsion solvent diffusion/evaporation method], taking different ratios of drug/polymer. Solvent systems consist of ethyl acetate and dichloromethane for microspheres and nanospheres, respectively. In the current study formulations were characterized by loading efficiency, yield, particle size, zeta potential, X-ray diffraction [XRD] and differential scanning calorimetry [DSC]. In microparticles, the best drug to polymer ratio was 0.8:1 [F[3]]. F[3] formulation had minimum burst effect [37.81%], high loading efficiency [95.88%]. In nanoparticles, F[4] formulation [0.4:1 drug/polymer ratio] showed high production yield [40.8%], loading efficiency [99.05%], low particle size [756 nm] and minimum burst effect compared with other nanoparticle formulations. The drug loaded composite microspheres [F[9]] showed minimum burst effect, acceptable release and mean particle size 17.696 micro m. The XRD and DSC showed stable character of theophylline in the drug loaded microspheres. The drug release was found to be diffusion and erosion controlled. The burst was significantly lower with composite microparticles and may be explained by lower diffusion of the drug from double polymeric wall formed by the nanoparticles matrix followed by another diffusion step through the microparticle polymeric wall
Subject(s)
Nanoparticles , Polyesters , X-Ray Diffraction , Calorimetry, Differential Scanning , EmulsionsABSTRACT
Cutaneous drug reaction seems to be relatively common The aim of the study was to recognize offending drugs, evaluate patients' characteristics and educate the patients to avoid selfadministration and re-administration of drugs. We retrospectively and prospectively analyzed data from Sina hospital in Tabriz [2000-2005] to determine the number of hospitalizations and visits with primary diagnoses of skin conditions that are often attributed to drugs. A physical examination was done by a dermatologist who completed a standardized questionnaire. Requested information included patient characteristics [associated disorders, severity scores], drug intake and characteristics of the skin reaction [type, course].Using statistical methods for surveys, we determined the demographic characteristics of patients with these diagnoses. Three hundred patients [148 males and 152 females] with cutaneous drug eruption were studied. The most common eruptions were erythroderma [41.3%] and maculopapular rash [26%] and the most common offending drugs were carbamazepine [28%], carbamazepinevalproate [20%] and Co-Ttrimoxazole-carbamazepine-diclofenac sodium combination [26.7%]. The highest number of the patients belonged to the age group of 30-39 years [15%]. The interval between developing lesions and intake of the offending drug varied from 1 day to 45 days. Drug reactions showed that 20-30% of the ADRs from anticonvulsants, 15-25% of the ADRS from sulfonamides, 10% of the ADRs from antibiotics, and 7% of the ADRs from non-steroidal antiinflammatory and anti-hypertensive drugs were dermatological. The pattern of ADRs and the drugs causing them is remarkably different in our population. Knowledge of these drug eruptions, the causative drugs and the prognostic indicators is essential for clinicians. It is recommended to advise patients to carry a card or some other form of an emergency identification in their wallets that lists drug allergies and/or intolerances, especially if they have had a severe reaction