Brinzolamide-Loaded Nanoemulsions: In vitro Release Evaluation

The aim of this investigation was to design and develop nanoemulsions (NEs) as novel ophthalmic delivery systems for brinzolamide (BZD). Phase behavior of quaternary systems composed of triacetin and CapryolTM 90 (selected oils, screened through the solubility studies), various surfactants (namely, Cremophor RH 40, Brij 35, Labrasol and tyloxapol), Transcutol P (as co-surfactant) and water at different surfactant/co-surfactant weight ratios (Rsm) was investigated by the construction of phase diagrams. Formulations were taken from the o/w NE region on the phase diagrams, depending on the extent of NE domain. The spontaneous emulsification method was used to prepare various formulations containing 0.4 wt% of the drug. The nanosized character of NEs was evaluated, the cumulative drug release from of the selected formulations was determined for a period of 6 h, using a dialysis sac technique and the release efficiency for NEs was calculated. The therapeutic efficacy of the selected BZD-loaded NEs to lower the IOP was assessed by the calculation of various pharmacodynamic parameters (ie., Emax, Tmax AUC0-6h). In all cases, the average size of the droplets was found to be less than 40 nm. In vitro release studies indicated that the release efficiency in most of the NEs was higher as compared to the BZD ophthalmic suspension. Comparison of the pharmacodynamics parameters confirmed the equivalent efficacy of most BZD formulations

Optimization of single-walled carbon nanotube solubility by noncovalent PEGylation using experimental design methods

In this study, noncovalent functionalization of single-walled carbon nanotubes (SWCNTs) with phospholipid-polyethylene glycols (Pl-PEGs) was performed to improve the solubility of SWCNTs in aqueous solution. Two kinds of PEG derivatives, ie, Pl-PEG 2000 and Pl-PEG 5000, were used for the PEGylation process. An experimental design technique (D-optimal design and second-order polynomial equations) was applied to investigate the effect of variables on PEGylation and the solubility of SWCNTs. The type of PEG derivative was selected as a qualitative parameter, and the PEG/SWCNT weight ratio and sonication time were applied as quantitative variables for the experimental design. Optimization was performed for two responses, aqueous solubility and loading efficiency. The grafting of PEG to the carbon nanostructure was determined by thermogravimetric analysis, Raman spectroscopy, and scanning electron microscopy. Aqueous solubility and loading efficiency were determined by ultraviolet-visible spectrophotometry and measurement of free amine groups, respectively. Results showed that Pl-PEGs were grafted onto SWCNTs. Aqueous solubility of 0.84 mg/mL and loading efficiency of nearly 98% were achieved for the prepared Pl-PEG 5000-SWCNT conjugates. Evaluation of functionalized SWCNTs showed that our noncovalent functionalization protocol could considerably increase aqueous solubility, which is an essential criterion in the design of a carbon nanotube-based drug delivery system and its biodistribution

An Investigation into the Effect of Various Penetration Enhancers on Percutaneous Absorption of Piroxicam

Abstract Achieving a desirable percutaneous absorption of drug molecule is a major concern in formulating dermatological products. The use of penetration enhancers could provide a successful mean for this purpose. The aim of this study was to evaluate the effect of incorporating a few common penetration enhancers (in different concentrations) into a 0.5% w/w piroxicam (model drug) gel formulation, on the permeability rate of drug through rat abdominal skin in vitro. For this purpose various concentrations of oleic acid (OA), urea (UR), lecithin (LEC) and isopropyl myristate (IPM) were used as the penetration enhancer. In order to investigate the effect of penetration enhancers used in this study on the permeability rate of piroxicam through sections of excised rat skin, Franz-type diffusion cells were employed. The receptor phase was constantly stirring 0.9% w/v sodium chloride solution at 32°C. At set intervals up to 8h, 5ml samples were removed from the receptor compartment and the amount of piroxicam permeated through the skin calculated by determining the UV absorbance of drug at 353 nm. Results show that among the penetration enhancers used, the use of OA at a concentration of 1.0% w/w had the greatest effect on the permeability rate of piroxicam, and produced the highest enhancement ratio among all the penetration enhancers examined. The other penetration enhancers used were found to have a far smaller effect on the permeability rate of piroxicam through rat skin. The enhancement ratio of the penetration enhancers used in the formulation of piroxicam gel were found to increase in the order of OA>> IPM > LEC > UR

An Investigation into the Optimization of Release Profile of Lithium Carbonate from Matrix-type Tablets Containing Carbopols, Pemulen and Eudragits

Abstract The influence of various polymers on the release rate of lithium carbonate from matrix-type tablets was investigated in an attempt to formulate a sustained release solid dosage form. For this purpose, tablets containing 450 mg of lithium carbonate along with various amounts of Carbopol 934P, 971P, 974P, Pemulen and Eudragit RLPO as retarding agents and inactive ingredients (e.g. PVP, Avicel or starch) were prepared using wet granulation technique. Tablets prepared were initially placed in a phosphate buffer solution for 7 h and those formulations from which a minimum of 80% lithium carbonate released, were selected for coating process. The amount of drug released was determined by using atomic absorption spectroscopy. The dissolution rate of enteric coated matrix-type tablets were then evaluated in both acidic and basic mediums (1 h and 11 h, respectively). The results showed that Pemulen and Carbopol 971P are not suitable polymers for preparing tablets with desirable release profile, at all concentrations examined. However, it was observed that Carbopol 934P, 974P and Eudragit RLPO are capable of producing tablets with desirable release pattern, at concentrations of 2, 1.5 and 3%, respectively. Tablets containing Eudragit RLPO were found to have the greatest drug release profile, while Carbopol 974P showed the slowest release rate

An Investigation into Improvement of Stability and Efficacy of Intravesical BCG Formulations Using Freeze-Drying Technique: Stability and efficacy of intravesical BCG formulations

Bacillus Calmette–Guérin (BCG) has been used as an intravesical product for the treatment of intermediate and high risk, non-muscle-invasive bladder cancer (NMIBC). Freeze drying technique is highly recommended for product development, however, the microorganism sensitivity to freezing and drying processes is a major chalenge which may lead to poor survival. To overcome this problem, the use of cryoprotectants in intravesical BCG formulation is required. This study was, therefre, planned to design a new formulation, using an attenuated strain of Mycobacterium bovis, which could be produced by freeze drying technique with the aim of prolonging its storage stability and increasing its efficacy as well as the ease of administration. For this purpose, sodium L-glutamate monohydrate (a commonly used stabilizer in domestic BCG suspension formulations) was replaced by lactose monohydrate. New intravesical BCG formulations, both in lyophilized and liquid forms, were eventually evaluated by moisture content assay, viable count assay, bacterial and fungal contamination, safety test and determination of bacterial concentration and O2 consumption. The results were compared with the data obtained for the conventional lyophilized and liquid products. Maximum survival rate was achieved in the presence of 10 % w/v lactose monohydrate for both liquid and lyophilized formulations when stored at less than -10 and 2-8C, respectively. In summary, the freeze-dried formulations developed with lactose monohydrate met the requirements of intravesical BCG in high viability and stability during storage. HIGHLIGHTS Lyophilization technique and lactose monohydrate as a protecting sugar were used to improve the stability, storage conditions, shelf-life and effcicay of intravesical BCG product. Maximum survival rate was attained for both liquid and lyophilized lactose-based formulations prepared with 10 %w/v lactose monohydrate and stored at less than -10 and 2-8°C, respectively. Freeze-dried products possessed higher stability and efficacy in comparison with corresponding liquid preparations. &nbsp

Brinzolamide-Loaded Nanoemulsions: In vitro Release Evaluation

Abstract The aim of this investigation was to design and develop nanoemulsions (NEs) as novel ophthalmic delivery systems for brinzolamide (BZD). Phase behavior of quaternary systems composed of triacetin and Capryol TM 90 (selected oils, screened through the solubility studies), various surfactants (namely, Cremophor RH 40, Brij 35, Labrasol and tyloxapol), Transcutol P (as co-surfactant) and water at different surfactant/co-surfactant weight ratios (R sm ) was investigated by the construction of phase diagrams. Formulations were taken from the o/w NE region on the phase diagrams, depending on the extent of NE domain. The spontaneous emulsification method was used to prepare various formulations containing 0.4 wt% of the drug. The nanosized character of NEs was evaluated, the cumulative drug release from of the selected formulations was determined for a period of 6 h, using a dialysis sac technique and the release efficiency for NEs was calculated. The therapeutic efficacy of the selected BZD-loaded NEs to lower the IOP was assessed by the calculation of various pharmacodynamic parameters (ie., E max , T max AUC 0-6h ). In all cases, the average size of the droplets was found to be less than 40 nm. In vitro release studies indicated that the release efficiency in most of the NEs was higher as compared to the BZD ophthalmic suspension. Comparison of the pharmacodynamics parameters confirmed the equivalent efficacy of most BZD formulations

Laccase Activity in CTAB-Based Water-in-Oil Microemulsions

Abstract The aim of this study was to develop a microemulsion system as a medium for laccasecatalyzed reactions. Phase behavior studies were conducted by constructing partial pseudoternary phase diagrams for systems comprising of cetyltrimethylammonium bromide (CTAB), various organic solvents as the oil phase (i.e., hexane, cyclohexane, heptane, octane, isooctane, toluene, isopropyl myristate), two co-surfactants (i.e., 1-butanol and 1-hexanol) and citrate buffer solution, at various surfactant/co-surfactant weight ratios (R sm ). A monophasic, transparent, non-birefringent area (designated as microemulsion domain) was seen to occur in some phase diagrams along the surfactant/organic solvent axis, the extent of which was dependent mainly upon the nature of co-surfactant and R sm . On each phase diagram, three different water-inoil (w/o) microemulsion systems with less than 50 wt% surfactant mixture and less than 20 wt% of aqueous phase were selected for laccase loading and activity measurements. Results revealed that the catalytic activity of laccase in CTAB-based w/o microemulsions decreased considerably, compared with its activity in the buffer solution, the extent of which depended upon the type of component and their compositions in the microemulsions. It was suggested that the conformational changes due to the electrostatic interactions between the cationic head group of CTAB and the negative enzyme might be the reason for the reduction of laccase activity, once entrapped in the microemulsion

Particle size analysis of concentrated phospholipid microemulsions: II. Photon correlation spectroscopy

The solvated droplet size of concentrated water-in-oil (w/o) microemulsions prepared frome egg and soy lecithin/water/isopropyl myristate and containing short-chain alcohol cosurfactants has been determined using photon correlation spectroscopy (PCS). The effect of increasing the water volume fraction (from 0.04 to 0.26) on the solvated size of the w/o droplets at 298 K has been investigated at 4 different surfactant/cosurfactant weight ratios (Km of 1∶1, 1.5∶1, 1.77∶1, and 1.94∶1); in all cases the total surfactant/cosurfactant concentration was kept constant at 25% w/w. In the case of the microemulsions prepared from egg lecthin, the diffusion coefficients obtained from PCS measurements were corrected for interparticulate interactions using a hard-sphere model that necessitated estimation of the droplet volume fractions, which in the present study were obtained from earlier total intensity light-scattering (TILS) studies performed on the same systems. Once corrected for hard-sphere interactions, the diffusion coefficients were converted to solvated radii using the Stokes-Einstein equation assuming spherical microemulsion droplets. For both egg and soy lecithin systems, no microemulsion droplets were detected at water concentrations less than 9 wt% regardless of the alcohol and Km used, suggesting that at low concentrations of added water, cosolvent systems were formed. At higher water concentrations, however, microemulsion droplets were observed. The changes in droplet size followed the expected trend in that for a fixed Km the size of the microemulsion droplets increased with increasing volume fraction of water. At constant water concentration, droplet size decreased slightly upon increasing Km. Interestingly, only small differences in size were seen upon changing the type of alcohol used. The application of the hard-sphere model to account for interparticulate interactions for the egg lecithin systems indicated that the uncorrected diffusion coefficients underestimated particle size by a factor of slightly less than 2. Reassuringly, the corrected droplet sizes agreed very well with those obtained from our earlier TILS study