Effect of non-phospholipid-based cationic and phospholipid-based anionic nanosized emulsions on skin retention and anti-inflammatory activity of celecoxib.

CONTEXT: Celecoxib (CXB, 0.2 g)-loaded anionic and cationic nanosized emulsions were prepared by a well-established combined emulsification method. OBJECTIVES: To investigate the effect of non-phospholipid-based cationic and phospholipid-based anionic emulsions on skin retention and anti-inflammatory activity of CXB. METHODS: Using Keshary-Chien diffusion cells with cellulose acetate membrane or excised rat skin, in vitro release and skin retention of CXB from solution and emulsions were studied. The anti-inflammatory activity was evaluated by the carrageenan-induced hind paw edema method in Wistar rats. RESULTS: The amount of drug released through artificial membrane has decreased from 122.00 ± 0.70 µg/cm(2) for the CXB solution to 55.80 ± 0.70 µg/cm(2) for anionic emulsion, and then further decreased to 24.79 ± 0.90 µg/cm(2) for cationic emulsion. The JSS value obtained with solution, anionic, and cationic emulsions were 6825.79 ± 920.86, 2513.15 ± 382.71, and 1925.67 ± 147.42, respectively. Cationic emulsion showed a significantly higher level (P ≤ 0.05) of drug accumulation in full-thickness rat skin than anionic emulsion, and a substantially lesser percentage inhibition of edema values compared with both solution and anionic emulsion. DISCUSSION AND CONCLUSION: Sustained drug release together with increased skin accumulation and simultaneously decreased skin permeation as observed with cationic emulsion should substantiate its suitability as a topical delivery vehicle for CXB.

In vitro evaluation of chitosan coated- and uncoated-calcium alginate beads containing methyl salicylate-lactose physical mixture.

CONTEXT: Methyl salicylate-lactose physical mixture (1:1 and 1:1.5 ratios) was incorporated into calcium alginate beads by a coacervation method involving an ionotropic gelation/polyelectrolyte complexation approach. OBJECTIVES: This study aims to determine the influence of chitosan coating over the beads on drug entrapment efficiency (DEE) and release characteristics in artificial saliva compared to that of the uncoated beads. RESULTS AND DISCUSSION: Changes in formulation parameters (gelation time, concentrations of Ca(2+) and alginate) resulted in decrease in DEE of chitosan-uncoated beads (p < 0.05). This is due to the combined effects of drug leach-out from the physical mixture by Ca(2+) ions, alginate gel matrix cross-linking and free drug diffusion from chitosan-uncoated beads. However, an increment in the DEE was seen for chitosan-coated beads. A rapid drug release profile was noted for uncoated beads, but for chitosan-coated beads a sustained release profile was depicted depending upon the coating conditions. Chitosan-coated beads had reduced swelling and erosion properties and thus behaved as a physical barrier to drug release. Shifting from anomalous transport type to Fickian transport confirmed the formation of physical barrier onto chitosan-coated beads. CONCLUSION: Calcium alginate beads could be used as a controlled-release system for methyl salicylate-lactose physical mixture.

In vitro and in vivo evaluation of hydrophilic and hydrophobic polymers-based nicorandil-loaded peroral tablet compared with its once-daily commercial sustained-release tablet.

CONTEXT: Hydrophilic and hydrophobic polymer-based nicorandil (10 mg)-loaded peroral tablets were prepared using the wet granulation technique. The influence of varying amounts of hydroxypropyl methylcellulose (HPMC) (30-50 mg), ethylcellulose (2-4 mg), microcrystalline cellulose (5-20 mg) and Aerosil® (5-12 mg) in conjunction with the constant amounts (3 mg) of glidant and lubricant (magnesium stearate and talc) on the in vitro performances of the tablets (hardness, friability, weight variation, thickness uniformity, drug content, and drug release behavior) were investigated. OBJECTIVE: The objectives of this study were (i) to select a nicorandil-loaded peroral tablet that matched the in vitro dissolution profile of once-daily commercial sustained-release tablet, and (ii) to compare the in vivo sustaining/controlling efficacy of the selected peroral tablet with that of its commercial counterparts. RESULTS AND DISCUSSION: Because the nicorandil (10 mg)-loaded tablet prepared based on F-IX composition (50 mg HPMC, 4 mg ethylcellulose, 10 mg MCC and 3 mg glidant and lubricant) showed a release profile comparable to that of the Nikoran® OD SR tablet release profile, the tablet with this composition was considered to be the optimized/selected formulation and, therefore, was subjected to stability study and in vivo study in rabbits. Despite of the higher C(max) and AUC values obtained with the optimized tablet, there was no sign of difference between the optimized- and Nikoran® OD SR- tablets following a single-dose crossover oral administration into rabbit. CONCLUSION: The optimized tablet could be used as an alternative to the commercial once-daily tablet.

Formulation and Evaluation of Hydroxypropyl Methylcellulose-based Controlled Release Matrix Tablets for Theophylline.

The objectives of the study were to formulate hydroxypropyl methyl cellulose-based controlled release matrix tablets for theophylline with varying drug:polymer ratios (1:1 and 1:2) and differing tablet hardness (5, 6 and 7 kg/cm(2)), and to evaluate the tablet's physico-chemical properties such as hardness, uniformity of weight, friability, drug content and in vitro drug release. Initially, granules were made by wet granulation technique and evaluated for angle of repose, bulk density, tapped density, bulkiness, compressibility index and hausner ratio. The results indicate good flow property of the granules and thus, the evaluated tablet physical properties were within the acceptable limits. The FT-IR study for the F-6 formulation showed that there was no interaction between the drug and the polymer. In vitro release studies were performed using Disso-2000 (paddle method) in 900 ml of pH 7.4 at 50 rpm. The result indicated that at high drug:polymer ratio (1:2) and hardness value 7 kg/cm(2), prolonged drug release was observed than the low drug: polymer ratio (1:1) and hardness values (5 and 6 kg/cm(2)). The release kinetics was found to follow korsmeyers-peppas model and the mechanism of drug release was by non-fickian or anomalous diffusion. The F-6 formulation was chosen for stability studies. F-6 formulation was stable when it was kept at different temperatures for a period of 6 months.

Stability assessment of injectable castor oil-based nano-sized emulsion containing cationic droplets stabilized by poloxamer-chitosan emulsifier films.

The objectives of the present work were to prepare castor oil-based nano-sized emulsion containing cationic droplets stabilized by poloxamer-chitosan emulgator film and to assess the kinetic stability of the prepared cationic emulsion after subjecting it to thermal processing and freeze-thaw cycling. Presence of cryoprotectants (5%, w/w, sucrose +5%, w/w, sorbitol) improved the stability of emulsions to droplet aggregation during freeze-thaw cycling. After storing the emulsion at 4 degrees C, 25 degrees C, and 37 degrees C over a period of up to 6 months, no significant change was noted in mean diameter of the dispersed oil droplets. However, the emulsion stored at the highest temperature did show a progressive decrease in the pH and zeta potential values, whereas the emulsion kept at the lowest temperatures did not. This indicates that at 37 degrees C, free fatty acids were formed from the castor oil, and consequently, the liberated free fatty acids were responsible for the reduction in the emulsion pH and zeta potential values. Thus, the injectable castor oil-based nano-sized emulsion could be useful for incorporating various active pharmaceutical ingredients that are in size from small molecular drugs to large macromolecules such as oligonucleotides.

Formulation and Evaluation of Theophylline Controlled Release Matrix Tablets using Guar gum

Theophylline controlled release matrix tablets were prepared with guar gum in two ratios and with three different hardness of 5, 6 and 7kg/cm2. Theophylline controlled release granules were prepared and evaluated for the angle of repose, bulk density, tapped density, compressibility index and hausners ratio. All the formulation showed good flow properties. The compressed tablets were evaluated for the hardness, uniformity of weight, friability, drug content and invitro dissolution studies. All the formulations showed compliance with pharmacopial standards. There was no interaction between drug, polymer and other excipients. It was confirmed by FTIR studies. Among all the formulations F6 (i.e. polymer ratio1:2 and hardness 7kg/cm2) showed prolong release when compare to other formulations. The drug release kinetics showed zero order. The optimum formulation (F6) was stable when it was stored at 40 + 20 C, 280 + 20 C and at 450 + 20 C for 6 months(AU)

Manufacturing techniques and excipients used during the design of biodegradable polymer-based microspheres containing therapeutic peptide/protein for parenteral controlled drug delivery.

In the last couple of decades, use of biodegradable polymer-based microspheres has been recognized as an interesting and promising approach for parenteral controlled delivery of therapeutic peptide/protein, including antigens. The main objectives of this review are (i) to update the current state of art of manufacturing of peptide/protein-loaded microspheres through both conventional and newer microencapsulation techniques, and (ii) to bring into focus the various possible instability problems, and the investigated mechanistic ways to obviate the instability problems of peptide/protein drug during microspheres preparation as well as its release from the microspheres. The solubilization, stabilization, and preservation enhancing excipients that are used in peptide/protein-loaded microspheres are briefly overviewed.

Oil-in-water lipid emulsions: implications for parenteral and ocular delivering systems.

Lipid emulsions (LEs) are heterogenous dispersions of two immiscible liquids (oil-in-water or water-in-oil) and they are subjected to various instability processes like aggregation, flocculation, coalescence and hence eventual phase separation according to the second law of thermodynamics. However, the physical stability of the LE can substantially be improved with help of suitable emulsifiers that are capable of forming a mono- or multi-layer coating film around the dispersed liquid droplets in such a way to reduce interfacial tension or to increase droplet-droplet repulsion. Depending on the concentrations of these three components (oil-water-emulsifier) and the efficiency of the emulsification equipments used to reduce droplet size, the final LE may be in the form of oil-in-water (o/w), water-in-oil (w/o), micron, submicron and double or multiple emulsions (o/w/o and w/o/w). The o/w type LEs (LE) are colloidal drug carriers, which have various therapeutic applications. As an intravenous delivery system it incorporates lipophilic water non-soluble drugs, stabilize drugs that tend to undergo hydrolysis and reduce side effects of various potent drugs. When the LE is used as an ocular delivery systems they increase local bioavailability, sustain the pharmacological effect of drugs and decrease systemic side effects of the drugs. Thus, the rationale of using LE as an integral part of effective treatment is clear. Following administration of LE through these routes, the biofate of LE associated bioactive molecules are somehow related to the vehicles disposition kinetics inside blood or eyeball. However, the LE is not devoid from undergoing various bio-process while exerting their efficacious actions. The purpose of this review is therefore to give an implication of LE for parenteral and ocular delivering systems.

Rare cause for short stature--Kallmann's syndrome--a case report.

Kallmann's syndrome is a neuroendocrine disorder, characterized by hypogonadotropic hypogonadism with hyposmia. We report a 27 year old male who presented with short stature and pain in the lumbar region. On detailed evaluation he had growth retardation, features of hypothalamic hypogonadism as evidenced by endocrimological tests and anosmia since birth. He had co-existent caries spine T10,T11 causing pain in the lumbar region-MRI brain showed normal olfactory pathway while the response to nasal stimulants was markedly attenuated. We present this case for its very care occurrence in the eastern part of the world and the typical feature being normal MRI brain with functional defect of the olfactory pathway.

Studies on in vitro release behaviour of indomethacin-loaded polystyrene microparticles.

Indomethacin-loaded polystyrene microparticles were prepared by emulsion-solvent evaporation method from an aqueous system. The effect of different parameters like concentration of aqueous phase emulsion stabilizer, volume of the organic disperse phase and initial drug loading on drug content and release of drug were investigated. Keeping the drug-polymer ratio constant, variation in the concentration of emulsion stabilizer and volume of the organic disperse phase did not produce any significant change either in the actual drug content or in the drug release. The initial drug loading, however, greatly influenced the drug release which, as revealed by different analyses, was due to the presence of drug in different physical forms in the microparticles. Physical characterization using thin layer chromatography and infrared spectroscopy apparently revealed the absence of drug degradation and sizeable interaction between the drug and the polymer. Regardless of lack of interaction, thermodynamic properties such as solubility of the drug in the polymer and fraction of the drug present in crystalline form were determined by using differential scanning calorimetry and was further substantiated with scanning electron micrography and X-ray diffraction analysis.

Studies on the in vitro release characteristics of ibuprofen-loaded polystyrene microparticles.

Ibuprofen-loaded polystyrene microparticles were prepared by the emulsion-solvent evaporation process from an aqueous system. The effects of different parameters on the drug content and on the release of the drug from the microparticles were investigated. The drug content, in all the formulations, was less than the theoretical drug loading. The lower drug content was due to drug partitioning to the external aqueous phase during formulation. Statistical analysis revealed that the variation in the concentrations of the emulsion stabilizer and the organic disperse phase volume did not significantly alter the release of the drug. Although an increase in drug loading increased drug release from the microparticles, a biphasic linear relationship was observed between the time required for 50% drug release and the drug loading. The effect of size of the microparticles on drug release was more important for the low drug-loaded microparticles than that for the high drug-loaded microparticles. Such release behaviour from the microparticles was explained on the basis of the morphological structure of the microparticles.

Effect of production variables on the physical characteristics of ibuprofen-loaded polystyrene microparticles.

Ibuprofen-loaded polystyrene microparticles were prepared by the emulsion-solvent evaporation method from an aqueous system containing methylcellulose as the emulsion stabilizer. The effect of production variables on the formation and the physical characteristics of the microparticles were studied. While an increase in stirring speed, concentration of emulsion stabilizer up to a critical value and disperse phase volume decreased the mean diameter of the particles, increase in drug loading and concentrations of emulsion stabilizer beyond the critical value tended to increase in size. The microparticles, except those prepared at higher stirring speeds, and with higher disperse phase volumes and drug-loads, were found to be spherical.