A NOVEL DESIGN AND EXPANSION OF NANO SUSPENSION
Kumkum Sarangdevot1*, Bhawani Singh Sonigara2, Priyadarshani Kamble 2, Ravindra Kamble2,
1. Pacific college of Pharmacy, Udaipur Rajasthan India.
2. B N College of Pharmacy, Udaipur Rajasthan India.
Solvent anti solvent precipitation Method are used . In this Carbamazepine was dissolved in the solvent (ethanol) at concentrations ranging from 5 to 15 mg/ml. The Purpose of the present work is to enhance solubility of carbamazepine a class II drug by nanosuspensions technology. In this Carbamazepine was dissolved in the solvent (ethanol) at concentrations ranging from 5 to 15 mg/ml. The experimental results had shown promising observations in terms of pH, drug content, entrapment efficacy and % transmittance. Consequently nanosuspensions represent a promising alternative to current delivery systems aiming to improve the biopharmaceutical performance of drugs with low water solubility. The polymer can serve as potential polymer for formulating various drug loaded nanosuspensions.
Key words: Carbamazepine, Nanoparticles, Modified Precipitation method.
Solubility is the property of a solid, liquid, or gaseous chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent. The solubility of a substance fundamentally depends on the solvent used as well as on temperature and pressure. The extent of solubility of a substance in a specific solvent is measured as the saturation concentration where adding more solute does not increase its concentration in the solution 1.
The solvent is generally a liquid, which can be a pure substance or a mixture of two liquids. One may also speak of solid solution, but rarely of solution in a gas. The extent of solubility ranges widely, from infinitely soluble (fully miscible) such as ethanol in water, to poorly soluble, such as silver chloride in water. The term insoluble is often applied to poorly or very poorly soluble compounds 2.
Solubility occurs under dynamic equilibrium, which means that solubility results from the simultaneous and opposing processes of dissolution and phase joining (e.g., precipitation of solids). Solubility equilibrium occurs when the two processes proceed at a constant rate. Under certain conditions equilibrium solubility may be exceeded to give a so-called supersaturated solution, which is metastable 3.
Solubility is not to be confused with the ability to dissolve or liquefy a substance, since these processes may occur not only because of dissolution but also because of a chemical reaction. For example, zinc is insoluble in hydrochloric acid, but does dissolve in it by chemically reacting into zinc chloride and hydrogen, where zinc chloride is soluble in hydrochloric acid. Solubility does not also depend on particle size or other kinetic factors; given enough time, even large particles will eventually dissolve 4 .
IUPAC defines solubility as the analytical composition of a saturated solution expressed as a proportion of a designated solute in a designated solvent. Solubility may be stated in units of concentration, molality, mole fraction, mole ratio, and other units 5.
Materials and Methods
2.1 Materials: Active Pharmaceutical Ingredients Carbamazepine (API) was Procured by Glenmark Pharma, Mumbai and other chemicals Ethanol Absolute, Hydroxy propyl Methyl cellulose 15000 cps, Lacithin, Dimethyl Sulphoxide(DMSO) etc was acquire from Central Drug House Delhi, India and VAV Life Scince Pvt ltd Mumbai India respectively.
2.2 Preformulation Studies
Various determinant factors that are applied to obtain the initial but crucial information required for the actual development process and the evaluation of the developed formulations were carred out during pre-formulation studies.
2.3. Identification of drug: Calibration curve of Carbamazepine in Water & 0.1 N Con.HCL
- Standard Calibration curve of Carbamazepine : The standard Calibration curves in two different media viz.,Water & 0.1 N Con.HCL were prepared by UV Spectroscopy using a doudle beam UV-VIS spectrophotometar (Shimadzu, model 1700).Graphs between drug concentration and absorbanc valuse determined at the λmax. were plotted in both the selected media.
- Preparation of stock solution (100 µg/ml): Accurately weighed quantity of 10 mg Carbamazepine was transferred into 100ml volumetric flask and dissolved and diluted up to the mark with Water to give a stock solution having strength 100µg/ml .
- Scanning of drug for determination of Absorption maxima (λmax): From the stock solution, 1ml was pippetted in 100ml volumetric flask. The volume was made up to 10 ml with water. The resulting solution containing 10 µg/ml was scanned between 200-400 nm. The λmax was found to be 285 nm was taken as analytical wavelength. UV spectrum is given in figure
- Preparation of different concentration sample solution : Different dilution viz., 1,2,3,4,5,6,7,8,9,and 10 µg/ml solution were prepared with Water & 0.1N HCL from the stock solution in 10 ml volumetric flask
2.4 Method for Solubility Studies of Carbamazepine
The solubility of Carbamazepine in various components (Actone, Water, Methanol, Ethanol, Benzene, Dimethyl Sulphoxide Tween 80, Haxan) was determined by using shake flask method. Briefly an excess amount of Carbamazepine was added to each vial containing 5ml of selected vehicle i.e. Actone, Water, Methanol, Ethanol, Benzene, Dimethyl Sulphoxide, Tween 80, Haxan Mixtures were shaken for 36 hrs in an isothermal shaker (Remi,Mumbai,India),maintained at 37±1⁰C,followed by centrifugation at 5,000 rpm for 15 min and filtration through membrane filter (0.45µm,13mm; pall Life Science, Mumbai, India).The concentration of the Carbamazepine in the filtrate was determined at 285 nm by UV Spectro-photometric method .
2.5 Partition coefficient
Partition coefficient of drug was determined in octanol-water system. The aqueous andnon-aqueous phases, water and octnol respectively, were mutually saturated before use by talking them together in 1:1 v/v ratio and overnight shaking on the water bath shaker. Both phases were separated by employing separating funnels. The presaturated organic layer (octanol) was used for partitioning studies. The stock solution of drug was prepared by dissolving approximately 10 mg of drug in 100 ml of organic phase. The same solution was analyzed prior to the partitioning study. Subsequently, 2 ml of organic phase (cosntaining 0.2 mg Drug) was taken in 10 ml screw capped tube and 2ml water added. These two pre-saturated phases were shaken for 24 hrs on a water bath at 37 c. the mixture was subsequently centrifuged to separate the aqueous and non-aqueous phases. The two phases were separately analyzed for carbamazepine at spectrophotomatric maxima the partition coefficient of drug Ko/w was calculated using following formula
Ko/w =concentration in octanol / conc. in distilled water
2.6 Formulation Development:
Solvent anti solvent precipitation Method Carbamazepine was dissolved in the solvent (ethanol) at concentrations ranging from 5 to 15 mg/ml. The syringe was filled with the prepared solution and secured onto a syringe pump. Drug solution was quickly injected at a flow rate (from 2 to 10 ml/min) into the antisolvent (deionized water) under magnetic stirring (200 to 1000 rpm). The solvent to antisolvent volume ratios used were 1:10, 1:15 and 1:20. The Carbamazepine particles precipitated were filtered and vacuum dried. To investigate the effect of a water-soluble polymer (PVP and PEG), PVP or PEG was dissolved in water at the concentration of 5 mg/ml and then used as the “antisolvent”. The rest of the procedure was the same as above to obtain Carbamazepine particles with PVP or PEG.
2.7 Evaluation parameters of Nanosuspension particle size and size distribution
Particle size and shape of the formulated microcapsules was determined by using Optical Microscope. The mean particle size and the width of particle size distribution (called Polydidpersity Index) are determined by Photon Correlation Spectroscopy104 (PCS). Particle size and polydispersity index (PI) governs the saturation solubility; dissolution velocity and biological performance. It is proved that change in particle size changes saturation solubility and dissolution velocity. PCS measures the particle size in the range of 3nm- 3 µm only. PI governs the physical stability of nanosuspension and should be as low as possible for long-term stability. (Should be close to zero). PCS is a versatile technique but has low measuring range. In addition to PCS analysis nanosuspensions are analyzed by Laser Diffractometry (LD). LD measures volume size distribution and measures particles ranging from 0.05- 80μm upto 2000µm. Atomic Force Microscopy105 is used for visualization of particle shape.
RESULT AND DISCUSSION
3.1 Determination of Absorption maxima (λmax) in Water:
The stock solution was Prepared as per the method described in methodology section and scanned by UV-Visible spectrophotometer. The λmax was found to de 285 nm was taken as analytical wave length. Calibration curve was plotted of carbamazepine in 0.1N HCL and Water.
Figure 1: Calibration Curve in 0.1N HCL
Figure 2: Calibration Curve of Carbamazepine in 0.1N HCL
The liner regression analysis was done on absorption data point are shown in table No. 1
Table 1 :Parameters liner regression analysis 0.1N HCL
|Beers Law Limits (µg/ml)||0.1-1|
Figure 3: Calibration Curve of Carbamazepine in Water
The linear regression analysis was on done on absorption data point are shown in table No. 2
Table 2: Parameters liner regression analysis in water
|Beers Law Limits(µg/ml)||1-10|
The solubility of Carbamazepine in various components (Actone, Water, Methanol, Ethanol, Benzene, DMF, DMSO, Tween 80, Haxan) was determined by using shake flask method. The concentration of Carbamazepine in the filtrate was determined at 285 by UV Spectrophotometric method.
Table 3 : Solubility of Carbamazepine in various components
|Component||Carbamazepine Saturated Solubility|
3.3 Partition Coefficient
The partition coefficient was determined by the shake flask or tube method and measuring the distribution of the solute is by US Spectroscopy from 30 to 420 mins.
Figure 4: Calibration Curve of Carbamazepine
3.4 Evaluation drug Release Study
Nanosuspensions were Prepared and their Release studies. The optimized formulation showed near to 60 % release in 6 hr. The release profile of formulation is showed in Table 4 & figure 4.
Figure 5 Drug Release plot of Different formulation
Table 4: Evaluation drug release study of different formulation:
|Time in Min.||%CRD of disperse drug||% CRD of Nanosuspension||% CRD of coid Water||%CRD of Hot Water||%CRD of Water+sls|
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