Influence Of Various Formulation Factors Research Articles

Exemestane loaded polymeric nanoparticles for oral delivery

The aim of the present study was to develop Exemestane loaded polymeric nanoparticles for improved oral bioavailability of Exemestane. Exemestane loaded nanoparticles were prepared by solvent displacement method with Eudragit RL 100 and Eudragit L 100 as polymers and Pluronic® F-68 as surfactant. The influence of various formulation factors (drug: polymer ratio and concentration of surfactant) on particle size, size distribution, zeta potential, encapsulation efficiency, in vitro drug release were investigated. The mean particle size of optimized formulations F5 and F13 were found to be 98.19nm and 48.16nm respectively. Zeta potential of optimized formulations F5 and F13 were found to be +22mV and -25mV respectively. Fourier Transform Infrared Spectroscopy (FT-IR) study indicated that, there was no interaction between drug and polymers. Scanning electron microscopy (SEM) study revealed spherical morphology of the developed NPs. The results of the present investigation indicate that the formulations F5 and F13 can be considered as best among various formulations with respect to particle size, entrapment efficiency and in-vitro drug release. In conclusion, this study indicates the capability of Eudragit nanoparticles in enhancing the oral bioavailability of exemestane.

Sustained release spherical agglomerates of polymethacrylates containing mefenamic acid: in vitro release, micromeritic properties and histological studies

Mefenamic acid (MA) spherical agglomerates (SAs) were prepared with various polymethacrylates having different permeability characteristics (Eudragit RS 100, Eudragit RL 100 and Eudragit L 100) and also with combination of Eudragit RS 100 and Eudragit L 100 in different ratios. SAs were prepared by spherical crystallization method using ethanol/dichloromethane solvent (crystallization) system. The influence of various formulation factors on the encapsulation efficiency, as in vitro drug release, and micromeritic properties was investigated. Target release profile of MA was also drawn. The yields of preparation and the encapsulation efficiencies were high for all formulations. The shape and surface characteristics of SAs were observed by a scanning electron microscope. The particle sizes are in the range of 0.219 ± 0.1 to 0.482 ± 0.25 mm (mean ± confidence interval t95%). In addition, histological studies showed that the administration of MA in SAs containing Eudragit RS/L provided a distinct tissue protection in the stomach and duodenum. Differential scanning calorimetry and X-ray diffraction of powder studies showed that MA particles crystallized in the presence of polymethacrylates did not undergo structural modifications.

Controlled release hydrophilic matrix tablet formulations of isoniazid: design and in vitro studies.

The aim of the present investigation was to develop oral controlled release matrix tablet formulations of isoniazid using hydroxypropyl methylcellulose (HPMC) as a hydrophilic release retardant polymer and to study the influence of various formulation factors like proportion of the polymer, polymer viscosity grade, compression force, and release media on the in vitro release characteristics of the drug. The formulations were developed using wet granulation technology. The in vitro release studies were performed using US Pharmacopoeia type 1 apparatus (basket method) in 900 ml of pH 7.4 phosphate buffer at 100 rpm. The release kinetics was analyzed using Korsmeyer-Peppas model. The release profiles were also analyzed using statistical method (one-way analysis of variance) and f (2) metric values. The release profiles found to follow Higuchi's square root kinetics model irrespective of the polymer ratio and the viscosity grade used. The results in the present investigation confirm that the release rate of the drug from the HPMC matrices is highly influenced by the drug/HPMC ratio and viscosity grade of the HPMC. Also, the effect of compression force and release media was found to be significant on the release profiles of isoniazid from HPMC matrix tablets. The release mechanism was found to be anomalous non-Fickian diffusion in all the cases. In the present investigation, a series of controlled release formulations of isoniazid were developed with different release rates and duration so that these formulations could further be assessed from the in vivo bioavailability studies. The formulations were found to be stable and reproducible.

Preparation and In Vitro/In Vivo Evaluation of Gliclazide Loaded Eudragit Nanoparticles as a Sustained Release Carriers

ABSTRACTThe aim of this study was to formulate and optimize gliclazide-loaded Eudragit nanoparticles (Eudragit L100 and Eudragit RS) as a sustained release carrier with enhanced efficacy. Eudragit L 100 nanoparticles (ELNP) were prepared by controlled precipitation method whereas Eudragit RSPO nanoparticles (ERSNP) were prepared by solvent evaporation method. The influence of various formulation factors (stirring speed, drug:polymer ratio, homogenization, and addition of surfactants) on particle size, drug loading, and encapsulation efficiency were investigated. The developed Eudragit nanoparticles (L100 and RS) showed high drug loading and encapsulation efficiencies with nanosize. Mean particle size altered by changing the drug:polymer ratio and stirring speed. Addition of surfactants showed a promise to increase drug loading, encapsulation efficiency, and decreased particle size of ELNP as well as ERSNP. Dissolution study revealed sustained release of gliclazide from Eudragit L100 as well as Eudragit RSPO NP. SEM study revealed spherical morphology of the developed Eudragit (L100 and RS) NP. FT-IR and DSC studies showed no interaction of gliclazide with polymers. Stability studies revealed that the gliclazide-loaded nanoparticles were stable at the end of 6 months. Developed Eudragit NPs revealed a decreased tmin (ELNP), and enhanced bioavailability and sustained activity (ELNP and ERSNP) and hence superior activity as compared to plain gliclazide in streptozotocin induced diabetic rat model and glucose-loaded diabetic rat model. The developed Eudragit (L100 and RSPO) NP could reduce dose frequency, decrease side effects, and improve patient compliance.

Multivariate toxicity screening of liposomal formulations on a human buccal cell line

The influence of various formulation factors on the in vitro cellular toxicity of liposomes on human buccal cells (TR146), were studied by using the concept of statistical experimental design and multivariate evaluation. The factors investigated were the type of main phospholipid (egg-PC, DMPC, DPPC), lipid concentration, the type of charge, liposome size, and amount and nature of the charged component (diacyl-PA, diacyl-PG, diacyl-PS, stearylamine (SA), diacyl-TAP) in the liposomes. Both full factorial design and D-optimal designs were created. Several significant main factors and interactions were revealed. Positively charged liposomes were shown to be toxic. The toxicity of negatively charged liposomes was relatively low. Diacyl-TAP was less toxic than SA, and DPPC was less toxic than DMPC. Low level of positively charged component was favourable and essential when using egg-PC as the main lipid. The amount of negatively charged component, the liposome size, and the total lipid concentration did not affect the toxicity within the experimental room. DPPC appeared to be a good candidate when formulating both positively and negatively charged liposomes with low cellular toxicity. The concept of statistical experimental design and multivariate evaluation was shown to be a useful approach in cell toxicity screening studies.

In vitro and in vivo studies of ibuprofen-loaded biodegradable alginate beads

The irritation effects of ibuprofen, a widely used non-steroidal anti-inflammatory drug (NSAID), were evaluated on mouse gastric and duodenal mucosa when suspended in 0.5% (w/v) sodiumcarboxymethylcellulose (NaCMC) solution and loaded in alginate beads. The ionotropic gelation method was used to prepare controlled release alginate beads of ibuprofen. The influence of various formulation factors on the encapsulation efficiency, as in vitro drug release and micromeritic properties, was investigated. Other variables included the alginate concentration, percentage drug loading and stirring speed during the microencapsulation process. Scanning electron micrographs of alginate beads loaded with ibuprofen showed rough surface morphology and particle sizes in the range of 1.15 ± 0.4–3.15 ± 0.6 mm. The yield of microspheres, as collected after drying, was generally 80–90%. Formulation code H showing t50% value of 3.5 h was chosen for in vivo trials because of the appropriate drug release properties. For in vivo trials, free ibuprofen (100 mg kg−1), blank and ibuprofen (100 mg kg−1) loaded alginate beads (formulation code H) were suspended in 0.5% (w/v) NaCMC solution and each group was given to six mice orally by gavage. NaCMC solution was used as a control in experimental studies. In vivo data showed that the administration of ibuprofen in alginate beads prevented the gastric lesions.

Microencapsulation of ibuprofen and Eudragit® RS 100 by the emulsion solvent diffusion technique

The emulsion solvent diffusion was employed to prepare modified release microspheres of ibuprofen. The technique was optimised for the following processing variables: the absence/presence of baffles in the reaction vessel, agitation rate and drying time. Thereafter, the influence of various formulation factors on the microencapsulation efficiency, in vitro drug release and micromeritic properties was examined. The variables included the methacrylic polymer, Eudragit® RS 100, ibuprofen content and the volume of ethanol used during microencapsulation. The results obtained were then interpreted on a triangular phase diagram to map the region of microencapsulation, as well as those formulations that yielded suitable modified release ibuprofen microspheres.

Blaboration and Technological Characterization of Inert Matrix Tables of Careolol Hydrochloride

AbstractAn original method for elaborating inert matrix tablets made with different types and proportions of Budragit is presented. The influence of various formulation factors on technological properties of these matrix tablets were tested.