4. DESCRIPTION
The drug entities, which have dissolution rate limited bioavailability, are categorized under BCS class II. About 40% of new chemical entities discovered are water insoluble. The poor aqueous solubility of drugs leads to poor dissolution profile and hence low oral bioavailability. Thus, formulating a new water insoluble drug molecule is a tough challenge for pharmaceutical scientist. Various formulation parameters like aqueous solubility, photo stability, stability at ambient temperature and humidity, compatibility with solvent and excipient plays an important role in manufacturing of a successful formulation. The most vital properties related to the pharmaceutical active molecules are its aqueous solubility, dissolution rate and bioavailability. To overcome these vital problems of water insoluble drug candidates, various techniques like co-solvents, milling techniques, super critical processing, solid dispersions, with complexation and precipitation techniques are used. However, these techniques fail to fulfil the needs to equip the pharmaceutical industry with particle engineering technologies; as they are not applicable for drugs, which are insoluble in aqueous and organic solvents. Hence, nanosuspension (NS) is a novel technology introduced to enhance the dissolution and bioavailability of water insoluble active pharmaceutical ingredients.
Surfactants (inhibitors) are found to be toxic when used more than its limit. Most of them have their effect on skin and into the body. The synthetic surfactants like detergents used for long term in modern life causes skin irritation and leads to some degree of damage. When the surfactants enter in body, they damage the enzyme activity and thus disrupt the normal physiological function of body. When, synthetic surfactant show toxicity and get accumulated in human body, thus difficult to degrade. The order of toxicity is nonionic > cationic > anionic for membrane labializing effects. Use of natural surfactant would be a best option to replace the synthetic one for preparation of most of pharmaceutical formulations. Use of natural inhibitor is preferable due to low / no toxicity, cheap and biodegradation and easy availability. Latex of Jatropha curcas can serve a best inhibitor of natural origin. Latex is emulsion like sticky materials that oozes out from various plants after having a small tissue grievance and hastily coagulates when exposed to air. In the recent years, Jatropha is primarily famous for the production of biodiesel on larger amount with several medicinal applications. Major parts of Jatropha are used for the treatment of various veterinary and human ailments. Jatropha curcas belongs to the family Euphorbiaceous. Different parts of this plant viz. roots, leaves, latex, seed etc. have been traditionally used for various purposes including the medicinal use. The extract of J. curcas leaves and roots have some ethnomedical uses which includes antiseptic, purgative, haemostatic, remedy for cancer, as an abortifacient, and diuretics. According to Osoniyi and Onajobi, the nut of the plant has also been used traditionally for the treatment of many ailments including burns, convulsions, fever and inflammation. Latex contains alkaloids like jatrophine, jatropham and curcain with anti-cancerous properties. Latex is also used as disinfectant in mouth infections in children.
Nanosuspension is sub-micron colloidal dispersion of drug particles, which is stabilized by surfactant or stabilizers. It has two outstanding features: its ability to increase saturation solubility and consequently increase the dissolution velocity. Nanosuspension can be prepared by bottom up and top down technologies. In the bottom up technologies, the low water soluble drugs are dissolved in a solvent and then precipitated in different ways in a surfactant solution. The top down technologies are based on particle fragmentation to submicron units and include ball milling and high-pressure homogenization. Nanosuspension technology increases saturation solubility, and consequently increases the dissolution rate of the compound. This increase in the dissolution rate is an additional advantage exhibited by the greater surface area. That solves the problem of drugs which are poorly aqueous soluble and have less bioavailability. Nanosuspensions are less stable due to rapid aggregation of particle caused by Ostwald ripening. It's a process where difference in solubility with particle size leads to conversion of material from small to large particles, which accomplish increase

in mean particle size with time. Ostwald ripening can be inhibited by incorporating small amount of components with very low aqueous solubility. This incorporation leads to differences in composition between large and small particle during Ostwald ripening process. This difference counterbalance the driving force for Ostwald ripening and thus leads to termination. Thus, the invention concerns to development a stable lyophilized nanosuspension of BCS II drugs like felodipine to enhance its bioavailability and stability using J. curcas latex as a stabilizer or inhibitor. A. Characterization of Jatropha curcas latex Plant material
The plant was obtained from Kupwad, Sangli, Maharashtra, India and authenticated from Dr. M. Y. Gholekar-Bachulkar, a plant taxonomist from V. Y. college, Peth-vadgaon, Maharashtra, India. The fresh latex was collected in the month of September. The latex was collected by incising the bark of Jatropha shrub and was stored in glass vial containing few drops of 95% ethanol to prevent browning and oxidation. This milky white solution of latex is converted to dry powder at room temperature by spreading on sterilized glass petri dish for 24 hours. Dried latex was subsequently scrapped off carefully using sterilized glass slide and meshed to obtain finer powder. Study shows liquid latex loses all its activity within a week then dried latex powder. As a precaution step, gloves are worn while collecting the latex since the latex causes irritation to the skin. The powder of J. latex was stored at -20°C and is used for future studies (Figure 1). pH determination
The pH of the latex was determined by a digital pH meter. The pH meter was first calibrated using distilled water. The pH was determined by shaking 1 % dispersion of the sample in water for 5 min and the surface pH was noted. The pH was measured thrice and the average values are used for the data. Melting point
Melting point of the latex was determined by filling latex powder in capillary tube closed at one end. The capillary tube was placed in a melting point apparatus and the temperature at which powder melts was recorded. This was performed thrice and average value was noted. Melting point was confirmed by DSC. Foaminess
Foaminesss is the maximum capacity of foaming liquid to catch air. The foaminess is the height of foam produced after shaking the sample at a given period with moderate agitation. The foaming index of J. latex was determined by shaker bottle method. Test tube with 2.5 cm diameter and 100 cc volume capacity was used to measure the foaming index of latex. Sample with 0.1% concentration of powdered latex was used for test. The maximum foam formation capacity of latex was determined by shaking the solution very vigorously until no change in the total foam height was observed. The total foam height is recorded and the foaminess is calculated as:

Where e/: foaminess [-] Vfoam'- volume of foam after shaking [cc] liquid: volume of liquid placed in the shaking tube [cc]
To achieve full foam expansion, the total foam height must be less than 90% of the total height of the test tube. Solubility:
Solubility of dried powder latex was determined by gravimetric method wherein 1 g of sample was dispersed in different solvents like water, ethanol, acetone, chloroform, and methanol. Measuring Emulsification Activity and Stability of Jatropha Latex: The dried powder latex of Jatropha was diluted with water to make concentration 1 g/L based on its solid yield. The pH of solution was adjusted to 7-8. The emulsification activity and stability of latex was measured using a method reported by Lee et al (2008). To determine emulsification activity and stability of dried powder, 4ml of above prepared solution was

diluted with 1ml substrate (hexadecane or castor oil). The mixture was vigorously shaken for 2 min on vortex mixer. The mixture was kept standing for 10 min and the turbidity formed was measured at 425 nm using a UV/VIS spectrometer (Jasco V-630) with water as blank. The emulsification activity was the measure of absorbance. The absorbance was measured every 10 min. for an hour. The log of the absorbance was plotted over time and the emulsification stability was calculated as the slope of the graph. For the control test, the 4ml latex in the above protocol was replaced with 4ml water. Quality of surfactant
1. Acidic methylene blue solution:
In 50 ml water, 12 ml H2SO4 was slowly added and cooled. To cold solution, 0.03 g methylene blue and 50 g Na2S04 anhydrate was added and diluted to 1L. In test tube containing 10 ml methylene blue and 5 ml chloroform mixture, 5 ml of 1 % J.latex solution (surfactant) was added followed by vigorous shaking and kept steady until two layers separated. When chloroform layer (bottom layer) becomes blue, another 2-3 ml of the surfactant solution was added. Again, it was shaken and kept steady to form layers. The chloroform layers showed dark blue color while water layer was colorless, thus there is existence of anionic surfactant in the sample solution.
2. Thymol blue test:
The neutralized 5 ml of J. latex solution was added to 5 ml thymol blue solution and shaken vigorously to observe the colour of the mixture. Reddish-purple colour was developed which indicates anionic nature of J. latex solution. B. Preparation and characterization of lyophilized nanosuspension Docking tool and algorithm
Molecular docking is used to predict the virtual interactions between felodipine, jatropham and jatrophine, major constituent of Jatropha curcas latex. VLife MDS version 4.6 is a powerful tool used for molecular docking studies. The structures of both felodipine, jatopham and jatrophine were drawn in 2D and converted to 3D and were finally optimized for docking study. The docking algorithm Biopredicta is based on genetic algorithm method used to study and predict the binding mode of two compounds by optimizing their receptor-ligand binding geometry within their structures. This is a successful strategy used to search the docked conformer's space. The molecular interaction studies between felodipine and jatrophine was analysed to prove their ability to enhance its solubility and to stabilze the nanosuspension. Parameters observed were type and energy (Ei) of interactions. Particle size and size distribution
For the efficient size reduction of the drug particles, water soluble polymers and surfactants were used to inhibit the particle agglomeration of drug, along with improvement in its physicochemical characteristic. Influence of different stabilizers with different concentration was investigated in media milling method with a fixed concentration of the drug. The type of compound and their amount employed for stabilization has a prominent effect on particle size. Small particles, which spontaneously aggregate to decrease the surface energy, were stabilized using surfactants which forms layer on drug molecules. Three stabilizers (SLS, HPMC 6cps, and J. latex) were tested for their stabilization potential. Important function of stabilizer was that they form a substantial mechanical and thermodynamic barrier at the interface that retarded the approach and coalescence of individual nanoparticles. As data shown in Table 1 and Figure 3 it may be concluded that mean particle size varies with stabilizer as well as changing in the concentration of stabilizer, and formulation stabilized with J. latex (1:0.5) shows highest particle size reduction as compared to other assorted polymers.

Table 1. Effect of various stabilizers and their concentration on particle size and size
distribution.
Batch Code Stabilizer Drug to Stabilizer Ratio Mean Particle Size (nm)
FN1 SLS 1 0.5 545 ± 2.24
FN2 SLS 1 1 595 ± 2.56
FN3 J. latex 1 0.5 350 ±2.25
FN4 J. latex 1 1 325 ± 2.36
FN5 HPMC 1 0.5 445 ±2.21
FN6 HPMC 1 1 479 ± 2.03
Preparation of lyophilized nanosuspension
Felodipine (2 %w/v) was dispersed in a 10 ml aqueous solution containing varying ratio of sodium lauryl sulphate, hydroxy propyl methyl cellulose and latex of Jatropha curcas in 20 ml vial. The resulting coarse pre-dispersion was comminuted using zirconium oxide beads (milling media) on a magnetic stirrer (1 MLH, Remi Laboratory Instrument). The effect of stirring time and ratio of different size of zirconium oxide beads were optimized by keeping the drug: surfactant: milling media volume (1:1:50) (Batch FN4) as constant initially. Then the optimized conditions of stirring time and ratio of different size of zirconium oxide beads were used throughout the study to optimize concentration of HPMC 6cps, SLS and J. latex, and volume of milling media using 32 factorial designs to achieve minimum particle size. The stirring was continued for specific time at 800 rpm for the preparation of optimized nanosuspension formulation. Nanosuspension of felodipine was optimized for formulation parameters by 32 factorial design. The coded values and observations of the optimization process by 32 factorial design are tabulated in Table 2.
Table 2. 32factorial desien layout for optimization of felodinine nanosusnension.
Batch No. XI X2
FN1 0.5 50
FN2 0.5 40
FN3 0.5 60
FN4 1 50
FN5 1 40
FN6 1 60
FN7 1.5 50
FN8 1.5 40
FN9 1.5 60
XI - Concentration of Surfactant (J. latex) (% w/v) X2 - % v/v of Milling Media (Zirconium oxide beads)
Factorial Design A statistical model incorporating interactive and polynomial terms was used to evaluate the responses
A statistical model incorporating interactive and polynomial terms was used to evaluate the responses:
Y=b0+blXl+b2X2 +bl2XlX2+ bl 1 Xl2+ b22X22
Where, Y is the dependent variable, bO is the arithmetic mean response of the 9 runs, and bi is the estimated coefficient for the factor Xi. The main effects (XI and X2) represent the average result of changing one factor at a time from its low to high value. The interaction terms (X1X2) show how the response changes when 2 factors are simultaneously changed. The polynomial terms (XI2 and X22) are included to investigate nonlinearity. The optimized conditions of stirring time and ratio of different size of zirconium oxide beads were used throughout the study to optimize concentration of Jatropha latex and volume of milling media using 32 factorial designs to achieve minimum particle size. Lyophilization of nanosuspension
The optimized nanosuspension (FN4) was lyophilized using mannitol (3%) as cryoprotectant, optimized by using, various cryoprotectants in different concentrations. Vials containing

nanosuspension were freezed in deep freezer at -20°C for 24h (EIE, India) for primary
freezing. The vials (10ml) were then lyophilized by using Labconco FreezOne 2.5®
lyophilizer. The solvent was sublimed under a pressure of 0.0016 mmHg for 48 hrs.
pH of nanosuspension
Prepared nanosuspension was taken in 10ml beaker and pH was measured using pH meter
(Digital Instrument Corporation, India). Table 3 shows the pH of the nanosuspension before
and after addition of cryoprotectant.
Table 3. Shows results of following parameters

Sr. No. Parameters Results
1 Saturation .solubility Plain drug (Felodipine) 24.63ug/ml

Felodipine nanosuspension 206.54ug/ml
2 pH With mannitol 7.42

Without mannitol 6.71
3 Drug content 99.52%w/w
Saturation solubility
Saturation solubility depends on the temperature and the properties of the dissolutior medium. However, the saturation solubility is a function of the particle size below approximately 1-2 um. Saturation solubility of felodipine and lyophilized powder o: optimized nanosuspension formulation were carried out in phosphate buffer pH 6.8 for whicl 10 mg of drug and lyophilized powder (equivalent to 10 mg of drug) in 10ml phosphate buffei pH 6.8 were taken separately and were allowed to be stirred in an orbital shaker (37.0 ±1.0°C for 72 h. The stirred samples were further centrifuged at 5000 rpm for 30 minutes. The supernatant were collected and diluted with PBS pH 6.8 and absorbance was measured ai 238nm using UV-Visible spectrophotometer. The solubility was measured at 25°C. Drug content
Drug content in nanosuspension was carried out by taking lyophilized powder (equivalent tc 10 mg of drug) in methanol, shaken well; mannitol being slightly soluble in methanol it was centrifuged at 5000 rpm for 20min. The supernatants were diluted with methanol and the absorbance was measured at 238 nm. The drug content was calculated using the calibratior curve.
In vitro Dissolution studies
In vitro dissolution studies were performed using dialysis membrane technique. The preparec nanosuspension was poured in dialysis bags and were sealed on both sides. The bags were placed in beaker containing 100ml of phosphate buffer 6.8 pH used as the dissolutior medium. The entire system was kept at 37±0.2 °C with continuous magnetic stirring Dissolution was carried out on an equivalent of 10 mg of felodipine. Readings in triplicate were taken for each measurement. Samples (5ml) were withdrawn at regular intervals of 5 min for 60 min and replaced with fresh dissolution medium. Samples were filtered through 0.2u whatman filter paper and drug released was determined spectrophotometrically on Shimadzu UV-Visible spectrophotometer at 238 nm wavelength. FTIR study
FTIR spectra's of powdered latex, felodipine and lyophilized nanosuspension were recorded using Infrared spectrophotometer (JascoV-530 model). About 2 mg of sample was ground thoroughly with KBr; uniformly mixed sample kept in sample holder and spectra recorded over the wave number 400-4000 cm"1 on spectrophotometer (Fig. 4). Differential Scanning Calorimeter (DSC)
Thermal behavior of powdered latex, felodipine and lyophilized nanosuspension were analyzed by DSC on a Shimadzu differential scanning calorimeter (TA instruments, model SDT 2960, USA) equipped with intra cooler and refrigerated cooling system was used to analyze the sample. Powder X-Ray Diffraction (PXRD) PXRD patterns of- powdered latex. felodipine and lyophilized nanosuspension were

recorded at room temperature on X-ray diffractometer (Philips analytical XRD, PW 3710) with CuKa radiation (1.54 A), at 40 kV, 40 mA and passing through a nickel filter. The diffractometer was equipped with a 2q compensating slit and was calibrated for accuracy of peak positions with a silicon pellet. Samples were mounted on a 25-mm holder made of polymethyl methacrylate and were subjected to X-ray powder diffraction analysis in continuous mode with a step size of 0.01° and step time of 1 second over an angular range of 3 to 40° 2q. Sample holders were rotated in a plane parallel to their surface at 30 rpm during the measurements. Stability study
Stability of optimized nanosuspension formulation was evaluated by determining change in
particle size during storage at 2-8°C. Any change in particle size of nanosuspension
formulation was observed using Malvern Mastersizer 2000 at periodic time intervals.
Result and Discussion
Characterization of Jatropha curcas latex
Parameters Results
pH : 7.9
Melting point : 126
Solubility : Minimum solubility in water at pH 5.5 and increased solubility
at acidic and alkaline pH values, with maximum nitrogen
solubility at pH 10.5
Foaming index : 6.5
Quality of surfactant : Anionic surfactant Docking study
Molecular docking predicts the preferred orientation of one molecule into the second one, which is frequently used to predict the binding orientation of small drug candidates to their targets. Therefore, this method is suitable for the predicting the behavior of compounds through docking with receptor. The present study aims to predict the interaction between felodipine and jatrophine to predict the ability of Jatropha latex to inhibit ostwald ripening. The virtual interactions between felodipine and jatrophine are shown in Fig. 2. Interaction between jatrophine and felodipine contributes strong interaction with each other consuming very less energy for binding, with strong hydrogen, hydrophobic and Vander wall interactions with each other. Thus from this results one can predict that the strong hydrogen interaction between the felodipine and jatrophine can virtually increase the stability of nanosuspension. Particle size and Size distribution
The optimized batch (FN4) had a mean particle diameter (nm) of 210 nm with uniformity (absolute deviation from median value) 0.442 (before lyophilization) with 1 %w/v of stabilizer and 50%v/v particles. After lyophilization the mean particle diameter was still 212 nm with uniformity 0.962 (Table 4, 5). Increasing the media volume led to slightly higher particle diameters but did not significantly change by increasing the concentration of stabilizer. The lowest mean particle diameter was obtained at 8h milling in 50:50 ratio of milling media (Table 6). Further stirring increased the mean particle diameter of the felodipine nanosuspension. The resulting nanosuspension was of uniform particle size in the range around 200nm. The particle size distribution pattern of the optimized nanosuspension formulation is given in Fig. 3.
Table 4. Optimization of the parameters for the preparation of nanosuspension

Batch Cone, of Cone. (Zr02 Particle Uniformity Particle Uniformity
No. drug
(%w/v) Surfactant (J. latex) %v/v of Milling Media beads) size Before Freeze Drying
(nm) size after Freeze Drying
(nm)

FN1 1 0.5 50 875 0.456 899 0.258
FN2 1 0.5 40 712 0.358 733 0.252

FN3 1 0.5 60 862 0.542 880 0.342
FN4 1 1 50 347 0.442 355 0.962
FN5 1 1 40 390 0.247 410 1.25
FN6 1 1 60 425 0.325 450 0.356
FN7 1 1.5 50 553 0.471 593 0.247
FN8 1 1.5 40 600 0.512 625 0.325
FN9 1 1.5 60 610 0.256 666 0.852
Tab e 5. Effect of stirring time for the preparation of felodipine nanosuspension i
Batch. No. Time (h) Mean particle size (nm)
ST1 10Min. 19.95um
ST2 2 2.739um
ST3 4 784nm
ST4 6 626nm
ST5 8 328nm
ST6 10 338nm
ST7 12 356nm
Table 6. Effect of Ratio of beads for the preparation of felodipine nanosuspension
Batch. No. Ratio of beads (Zirconium Oxide) Mean particle size (nm)

Small Size (0.4-0.7mm) Big Size (1.2-1.7mm)

RBI 100 0 650±1.20
RB2 75 25 596± 1.36
RB3 50 50 345±1.45
RB4 25 75 426±1.24
RB5 0 100 583± 1.04
Factorial equation for particle size and size distribution
Results of the factorial design equation indicate that the XI (polymer-to-drug ratio) significantly affects the mean particle size (p<0.05). As increase the concentration of stabilizer, it increases the mean particle size, while increase in the media volume led to slight decrease in the mean particle diameter. The relationship between the selected dependent and independent variables was further elucidated using response surface plots as shown in Fig. 5 and 6. The stabilizer concentration is also an important parameter influencing crystal size. An appropriate stabilizer concentration was used for each drug concentration to achieve smaller particle size. This can be explained by complete adsorption of stabilizer on the crystal surface. Crystal was protected by the adsorbed stabilizers, and the amount of stabilizer should be sufficient for full coverage on the crystal surface to provide enough steric repulsion between the crystals. Insufficient surface coverage of stabilizer could result in rapid crystal growth and agglomeration, while high concentration of stabilizer could result in enhanced viscosity of the solution.
Mean Particle Size = 356.44+21.17X1 -114.33X2 + 43.83 X1X2 -316.33X12+ 17.50 X22 Scanning electron microscopy (SEM)
SEM images reveal a change in appearance of the surface upon formulating the nanosuspension. The altered shape might be due to coating of felodipine particles with a surfactant/stabilizer layer and creation of an amorphous surface layer due to the high attrition and shearing rate (Fig.7). Differential Scanning Calorimetry (DSC)
The DSC thermograms of plain drug and optimized nanosuspension formulation were taken on a Mettler DSC 20 differential scanning colorimeter between 30-200°C at a heating rate of 20°C/min. Pure felodipine showed melting point at 149.10°C corresponding to its melting point, whereasin the thermograph pattern of formulation showed no such peak (Fig. 8). It can

be concluded that the drug particles were absolutely bound by the surfactant molecules (Rahman, 2006). As shown in Fig. 8 in the DSC of formulation sharp transitions at 54.72°C and 185.62°C were observed which correspond to the melting points of (J. latex) and (mannitol) respectively. X-Ray diffraction
XRD was used to analyze potential changes in the inner structure of felodipine nanosuspension during the formulation. The extent of such changes depends on the chemical nature and physical hardness of the active ingredient. The Fig. 9 show XRD thermograph of pure felodipine powder, J. latex and optimized batch FN4 formulation respectively. The obtained patterns reveal that the drug crystallinity of nanosuspension formulation was affected significantly and drug was converted into amorphous form. Saturation solubility
The saturation solubility is equilibrium between dissolving molecules (dissolution pressure) and re-crystallizing molecules. The saturation solubility increases with decreasing particle size according to the Ostwald-Freundlich equation. The results of saturation solubility of plain drug (F) and lyophilized powder of the nanosuspension (Table 3) revealed a saturation solubility of 24.63 ug/ml (plain felodipine) and 206.54ug/ml (felodipine-nanosuspension). Thus, saturation solubility of felodipine as a nanosuspension is 9.20 folds higher than that of felodipine. In the present study, particle size of Felodipine has been reduced hence the saturation solubility is increased due to increasing the surface area of the reduced particles. Drug content
In nanosuspension formulation, the drug particles were reduced to nano sized. During the formulation process there was no any drug loss step involved, so theoretically the formulation was considered as being 100% drug content. As shown in Table 3 the drug content was found to be 99.52%w/w. In vitro dissolution
Dissolution studies were compared for pure drug, and optimized nanosuspension formulation. The amount of drug released from the optimized nanosuspension formulation was 95.14 ± 3.12 % within 20 min compared to amount of 1.54 ± 1.28 % of pure drug in phosphate buffer pH 6.8. The increase in accessible surface area to the dissolution medium and hydrophilic surfactant coating on the particle surfaces may be the reason for increase in dissolution rate. This enhanced dissolution rate can be attributed to the higher surface area of nanocrystals available for dissolution and the decreased diffusion layer thickness (Fig. 10). Stability Studies
During storage as aqueous dispersions, nanosuspension sometimes show physical instability cause by Ostwald ripening (Fig. 11). However, crystal growth does not play any role in storage of nanosuspension at room temperature or at 5°C over a period of months. To avoid aggregation, formulation should be transferred into a dry product, such as by lyophilization or spray drying. Nanosuspensions can easily lyophilized and are well re-dispersible. Stability study of nanosuspension formulation was carried out at 2-8°C. The optimized batch was stable up to 3 months with slightly increase in the particle size on storage up to 3 months (Table 7). The particle size distribution indicated uniformity initially but due to the storage the particles aggregation might have occurred and so particle size was increased and uniformity was reduced (Fig. 7).
Table 7. Particle diameter of the optimized batch (FN4) of lyophilized nanosuspension during storage at 2-8°C.

Time (Months) Mean Particle size (nm) Uniformity
Initial 347 0.442
1 345 0.356
2 342 0.258
3 345 0.945
.^

5. CLAIMS
We claim,
1. A nanosuspension comprising (a) a pharmaceutical active ingredient or nutraceutical active ingredient having low solubility i.e. felodipine; (b) at least one or more stabilizer selected from the group consisting of (i) sodium laurly sulphate (ii) hydroxy propyl methylcellulose; (iii) plant derived Jatropha curcas latex and (c) water.
2. According to claim 1, major conundrum associated with the nanosuspension is its stability. Particles in nanosuspension are more prone to aggregation due to ostwald ripening. Addition of inhibitor (stabilizer) in formulation having lesser aqueous
. solubility can inhibit Ostwald ripening.
3. According to claim 1, stability of nanosuspension can be improved by using a plant-derived stabilizer, which has ability to inhibit Ostwald ripening.
4. According to claim 2, the stabilizer herewith used to formulate the nanosuspension is dried latex of Jatropha curcas.
5. In addition stable nanosuspension was developed by wet milling technique using 32 factorial design.
6. According to claim 4, inhibitory effect of J. curcas was studied in comparison with hydroxy propyl methyl cellulose (HPMC) and sodium laurly sulphate (SLS).
7. According to claim 4, the ability of J. curcas to stabilize the nanosuspension was predicited by molecular interaction between the felodipine and latex using molecular docking.
8. According to claim 4, the prepared nanosuspension was lyophilzed and characterized to particle size, zeta potential, saturation solubility, dissolution rate, morphology study, in-vitro diffusion study, while initial crystalline state was evaluated by differential scanning calorimetry and powder x-ray diffraction study.
9. According to claim 4, stability studies shows J. curcas inhibits ostwald ripening with improved stabilization of nanosuspension in comparion with Sodium lauryl sulphate and Hydroxy propyl methyl cellulose.
10. According to claim 4, inhibition of ostwald ripening was attributed to molecular interactions like hydrogen bonding and hydrophobic bonding interactions between felodipine and latex.
11. According to claim 4, initial crystalline state of drug is preserved followed by particle size reduction, with increase in saturation solubility, dissolution velocity and diffusion rate of the drug from the nanosuspension than that of the plain drug suspension and marketed formulation.
12. J. curcas latex serves as natural inhibitor to prepare many formulations with minimized toxicity, as it is biodegradable and has low toxicity then synthetic inhibitors.