, Md. Irfan Uddin1
DEVELOPMENT AND EVALUATION OF MICROEMULSION FORMULATIONS OF LORNOXICAM
Md. Shahidul Islam*, Md. Irfan Uddin1
Department of pharmacy, University of Science and Technology Chittagong (USTC), Chattogram, Bangladesh.
Background and aims: Microemulsions (ME) basically are the mixture of oil, surfactant (SA) and water, with a co surfactant (Co-SA) in different ratio. This mixture is clear and stable. The final prepared fluid possesses low viscosity. ME are isotropic, stable transparent systems of with a droplets diameter>500 nm. Due to small droplets size, they may serve an excellent carrier for drugs having poor water solubility. Lornoxicam is derivative of allylamine, and is used orally in the treatment of hepatic failure, neutropenia.
Methods: In the present study an attempt was made to increase solubility of Lornoxicam by the means of ME formulations. Oil, surfactant and co-surfactant were selected based on their solubility criteria. Total 5 formulations were developed using water titration method. Prepared formulations were evaluated on different parameters.
Results: The percent transmission was found to be in the range of 98.48±0.15to 99.42±0.04. Refractive index for the micro emulsion formulations was found to be in the range of 1.3218±0.009 to 1.3720±0.021. Percent drug content was found to be in the range of 98.47±0.08 to 99.75±0.21. ME5 has shown faster drug release 91.2±0.06% in an in-vitro study of 4 hrs.
Conclusion: Study concluded that the means of microemulsions formulations solubility of Lornoxicam can be enhanced.
Keywords: Co-surfactant, Lornoxicam, microemulsions, surfactant, thermodynamics.
INTRODUCTION
A microemulsion is considered to be a thermo-dynamically or kinetically stable liquid dispersion of an oil phase and a water phase, in combination with a surfactant. The dispersed phase typically comprises small particles or droplets, with a size range of 5 nm-200 nm, and has very low oil/water interfacial tension1,2. Because the droplet size is less than 25% of the wavelength of visible light, microemulsions are transparent.
ME are clear systems of with a droplets diameter>500 nm3. Due to small droplets size, they may serve an excellent carrier for drugs having poor water solubility. Aqueous phase consists of salt(s), and/or other ingredients, while oil consists of hydrocarbons and olefins. There is need of high shear in the preparation of emulsions, but for ME, there is no need of high shear, they simply formulated by the mixing of different ingredients3,4,5. O/W microemulsion tends to increase solubility by changing in its dispersed phase and improve oral bioavailability by the means of increase in rate of absorption and its wettability6,7,8.
Lornoxicam is a nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class with analgesic (pain relieving), anti-inflammatory and antipyretic (fever reducing) properties9,10.
The aim of present study was to develop and evaluate microemulsion formulations of Lornoxicam to avoid first pass metabolism and to minimize the adverse effect on the g.i.t like mild dyspepsia and heartburn to ulceration and hemorrhage.
MATERIALS AND METHODS
Lornoxicam was obtained as the Gift samples from Incepta Ltd. Octanol, Span 80, and Tween 80 from Merck ltd, Mumbai, India. Castor oil, soyabean oil, linseed oil was obtained from USTC, Foys lake, Chittagong, Department of pharmacy.
Selection of the oil phase
Selection of the oil phase was based upon the maximum solubility of the drug. Different oils including castor oil, Capmul Pg-12, soyabean oil, Kollisolv GTA, MCT were taken for solubility studies. Based on the solubility Capmul Pg-12 was selected as the oil phase11.
Selection of surfactants and co surfactant
Solubility of Lornoxicam was checked in different surfactants and co surfactants. Emulsification efficiency of surfactants and co-surfactants to check their ability to emulsify selected oil. To determine the emulsification ability, equal amount of surfactant was mixed with drug and after proper dilution, it was monitored for transmittance at 638 nm using UV-Vis spectrophotometer. The ease of formation of emulsion was monitored by the number inversions of volumetric flask required to produce uniform emulsion. Similarly co surfactant were selected based on their ability to form stable and clear micro emulsion at a minimum concentration11.
Solubility analysis
About 10 gm of oil was accurately weighed in 25 ml glass beaker and 100 mg of Lornoxicam was added into it, followed by stirring on magnetic stirrer at moderate speed to dissolve the drug. When drug was dissolved completely another 10 mg Lornoxicam of was added and stirring was continued. Addition of drug was continued until the saturated solution is obtained. Finally, the total amount of drug consumed was determined by using UV-spectrophotometer at 250 nm. In the similar way solubility of Lornoxicam was checked in different surfactants and co-surfactants12,13.
Preparation of drug loaded microemulsion
Formulations were developed using water titration method. Predetermined amounts of Lornoxicam (100) mg was dissolved in the required quantity of Capmul Pg-12 (oil). Tween-80: (surfactant) and Propylene glycol (co-surfactant) were added to the above mixture in different ratio. Distilled water was added gradually with continuous stirring, which resulted in the formulation of a transparent and homogenous microemulsion14,15,16.
Characterization of micro emulsion
Percentage Transmittance
Transparency of micro emulsion formulation was determined by measuring percentage transmittance through U.V. Spectrophotometer at 638 nm with distilled water taken as blank and three replicates were performed for each sample17.
pH determination
The apparent pH of all micro emulsions was determined at 25°C by immersing the electrode directly into the micro emulsion using a digital pH meter18,19.
Refractive index
Refractive indices of the prepared micro emulsions were determined at 25°C by Abbe’s refractometer by placing one drop of micro emulsion on the slide20.
Viscosity measurement
Micro emulsions are generally low viscosity systems. The viscosity of the prepared micro emulsion was measured at 25°C at 60 rpm by LV spindle no. 63 using a Brookfield viscometer21.
Determination of drug Content in the Lornoxicam micro emulsion formulations
The drug content of the micro emulsion formulation was determined by dissolving 1 ml (equivalent to 10 mg drug) of the formulation in 10 ml of methanol. After suitable dilutions with methanol, absorbance was determined using the UV spectrophotometer keeping blank micro emulsion as control at wavelength 250 nm and three replicates were performed for each sample22.
Drug solubility study: Lornoxicam was added in excess to the optimized microemulsion
formulation as well as each individual ingredient of the formulation. After continuous stirring for 4 hours at room temperature, samples were withdrawn and centrifuged for 10 minutes. The amount of drug soluble in optimized formulation as well as each
individual ingredient of the formulation was calculated by subtracting the drug in the sediment from the total amount of drug added. The solubility of drug in microemulsion was compared with respect to its individual ingredients22.
In-vitro drug release: The diffusion study was carried out on a modified Franz diffusion cell of
volume 20ml. The receptor compartment was filled with 20 ml of Phosphate buffer (pH 7.4). The
donor compartment was fixed with cellophane membrane (Cut Off weight=1000 Da) contains
Lornoxicam microemulsion formulation (equivalent to 5 mg of drug) and plain drug solution separately. At predetermined time intervals samples were withdrawn from receptor compartment and analyzed for drug content by UV Spectrophotometer at 250 nm23.
Drug release kinetic data analysis:
Release data was evaluated through PCP disso software for the kinetic models. First order, and Peppas and Korsmeyer model were studied23.
RESULTS AND DISCUSSION
Solubility of the oil phase, surfactant and co-surfactant
Solubility of Lornoxicam was checked in different oil to select the oil for the preparation of micro emulsion formulation. On the basis of solubility Capmul Pg-12 was selected as the oil and on the basis of emulsification efficiency and solubility Tween 80 was selected as the surfactant and Propylene glycol as the co-surfactant. Given Lornoxicam sample has shown maximum absorption (λmax) at 250 nm. FTIR spectroscopy was used to detect any kind of interaction between Lornoxicam and used oil (Capmul Pg-12), surfactant (Tween 80), co-surfactant (Propylene glycol). No change in peak was found, that indicate compatibility between them.
Total five formulations were developed to enhance the solubility of the Lornoxicam. Prepared formulations were further studied for different parameters including percent transmittance, drug content, pH determination, refractive index, viscosity, drug release.
Percentage Transmittance
The percent transmission carried out on UV spectrophotometer at 638 nm was found to be in the
range of 98.48±0.15 to 99.42±0.04 for all which confirms good transparent nature of formulations.
pH determination
For the micro emulsion formulations, the pH value was found to be in the range of 3.34±0.18 to 4.22±0.22.
Refractive index
The refractive index for the micro emulsion formulations was found to be in the range of 1.3218±0.009 to 1.3720±0.021.
Drug Content
The drug content was found to be in the range of 98.47±0.08 to 99.75±0.21 in the micro emulsion formulations.
Viscosity
The viscosity was found to be in the range of 63.13±2.1 to 70.86±4.74 in the micro emulsion formulations. The viscosity of the micro emulsion increased with increasing concentration of the surfactant18.
Drug release studies
It was seen that after 4 hours of diffusion, the drug released from the formulation ME5 faster and more than that of the other ratios i.e., 91.2±0.06%.
Kinetic modelling for micro emulsion –
In present study PCP disso Version 2 software was used in for the estimation of release pattern. Models for the release kinetic profile are shown in Table 6.
In-vitro release data were plotted in 2 different models i.e. first, and Korsemeyer peppas. It was observed that release was governed by the diffusion process.
CONCLUSION
Due to small droplets size, they may serve an excellent carrier for drugs having poor water solubility. Aqueous phase consists of salt(s), and/or other ingredients, while oil consists of hydrocarbons and olefins. There is need of high shear in the preparation of emulsions, but for ME, there is no need of high shear, they simply formulated by the mixing of different ingredients. Present study concludes successful delivery of Lornoxicam by the means of micro emulsion formulations.
CONFLICT OF INTEREST
No conflict of interest associated with this work.
ACKNOWLEDGEMENT
The authors would like to acknowledge Department of pharmacy, University of Science and Technology Chittagong (USTC), Chattogram, Bangladesh to support this work.
REFERENCES