Solubility determinations were performed in triplicate according to the method of Higuchi and Connors (Higuchi and Connors, 1965). In brief, an excess amount of soliddispersion was taken into the conical flask to which 10 ml of distilled water were added. The samples were shaken at room temperature for 24 hr on the rotary shake and filtered through a whatman filter paper. The filtrate was suitably diluted and analyzed spectrophotometrically at the wavelength of 226 nm using a UV- VIS spectrophotometer.[16,17]
After the approval of institutional animal ethical committee the in-vivo absorption studies of meloxicam soliddispersion incorporated buccal patch was conducted on rabbits. Three male rabbits (Siegel et al., 1981) weighing 5.0, 5.5, and 6.0 kg of either sex were used for the release study of the meloxicam. The animals were fasted for overnight with adlibitum storing them in individual cages before the experiment was carried out. The rabbits were anesthetized with phenobarbital sodium IP (1 ml containing 200 mg) by intra peritoneal route. Patches of size 1 x 1 cm2 were cut and fixed on a cellophane paper which acted as a backing layer so that the drug release was made unidirectional and threads tied to it, so that the patches were easily removed from the buccal cavity. After 30 min. of the anesthetic injection, the patches were placed (separately) in the buccal cavity one at time. After a gap of 2 min. further patches were attached. The patches were taken out at 0.5,1, 2, 3, 4, 5, 6, 7 and 8 th hours the process was repeated two more times to validate the result. The patches were dissolved in 10 ml of phosphate buffer, pH 6.8. The drug remained unabsorbed was analyzed 19 at 362 nm.
Assessment of possible incompatibilities between an active drug substance and different excipients forms an important part of the preformulation stage during the development of solid dosage form. Differential Scanning Calorimeter allows the fast evaluation of possible incompatibilities, because it shows changes in the appearance, shift of melting endotherms and exotherms, and/or variations in the corresponding enthalpies of reaction. The DSC thermograms of pure drug and bestsoliddispersion were recorded. DSC study was performed for furosemide and soliddispersion of furosemide
For complete absorption and good bioavailability of orally administered drug, the drug must be dissolved in gastric fluids. Dissolution of drug is the rate-controlling step which determines the rate and degree of absorption. Drugs with slow dissolution rates generally show erratic and incomplete absorption leading to low bioavailability when administered orally. Since aqueous solubility and slow dissolution rate of BCS class II and class IV drugs is a major challenge in the drug development and delivery processes, improving aqueous solubility and slow dissolution of BCS Class II and Class IV drugs have been investigated extensively. Various techniques have been used in attempt to improve solubility and dissolution rates of poorly water soluble drugs which include soliddispersion, micronization, lipid based formulations, melt granulation, direct compaction, solvent evaporation, coprecipitation, adsorption, ordered mixing, solvent deposition inclusion complexation and steam aided granulation. In these techniques carrier plays an important role in improving solubility and dissolution rate 8 .
Dissolution rate of felodipine from all its solid dispersions has compared to the pure felodipine and physical mixture was found to have increased. Dissolution profile of all the solid dispersions was dependent on drug-excipient ratio. As the proportion of excipient in the soliddispersion increases then the dissolution rate also increases. A comparison of t 50 %, t 90 % and dissolution efficiency at 30 minutes (DE 30min. ) shows that the drug- excipient ration of 1:9 gives higher dissolution rates than all the other drug-excipient ratios. Further
Solubility is the major criteria to achieve the desired concentration of the drug in the systemic circulation. About 80% of the drugs are poorly soluble. To overcome such a problem, several techniques have been developed to enhance the solubility of those drugs. Among them, soliddispersion is one of the most promising and new technique which promotes the dissolution rate of water-insoluble drugs. For the pure drug, the percentage of drug release was found to be very less due to its poor solubility characteristic nature. Hence in order to improve the solubility nature, the drug was formulated as solid dispersions in two different methods i.e., physical method and kneading method by using various solubility enhancing polymers like PEG6000, PEG20000, HPMC E15, HPC LH21,β-CYCLODEXTRIN &, SOLUPLUS. It was clear that all the investigated soliddispersion capsules complied with the Pharmacopoeial requirements concerning their content uniformity, which was found to lie within the range of 93.15% to 98.73%. Based on mathematical data revealed from models, it was concluded that the release data were best fitted with First-order kinetics. Stability studies showed that there were no significant changes in the physical and chemical properties of a formulation F8 after 3 months.
Drug Content Analysis: Accurately weighed soliddispersion equivalent to 50 mg of Eluxadoline transferred to 100 ml volumetric flask and dissolved into 6.8 phosphate buffer and made volume with the same solution up to the mark. After suitable dilution, the absorbance of the above sample was measured at 243 nm using 6.8 phosphate buffer as a blank solution and then, by using calibration curve drug content of Eluxadoline was calculated 16, 17 .
The solubility behavior of drugs remains one of the most exigent aspects in formulation development.With the advent of combinatorial chemistry and high throughput screening, the number of poorly water soluble compounds has dramatically increased. Among all the newly discovered chemical entities, about 40-45% drugs fail to reach market due to their poor water solubility. Because of solubility problem, bioavailability of drugs gets affected and hence solubility enhancement becomes necessary. Solid dispersions have attracted considerable interest as an efficient means of improving the dissolution rate and hence the bioavailability of drugs. This article reviews the various preparation techniques, carriers used, advantages and limitations of solid dispersions and compiles some of the recent advances. There are various methods available to improve the solubility of the new drug in which soliddispersion emerged promising. A Soliddispersion generally composed of two components- the drug and the polymer matrix. Numerous methods are existing to prepare the solid dispersions such as melting method, solvent evaporation method, fusion method, kneading method, melting method, spray drying method, co-grinding method, lyophilization technique, hot melt extrusion, melt agglomeration, supercritical fluid (SCF) technology etc. Soliddispersion technologies are particularly promising for improving the oral absorption and bioavailability of BCS Class II drugs. The experience with solid dispersions over the last 10-15 years indicates that this is a very fruitful approach in improving the release rate and oral bioavailability of poorly water soluble drugs. Hence, this approach is expected to form a basis for the commercialization of many poorly water-soluble and water-insoluble drugs in their solid-dispersion formulations in the near future.
Vacuum grease was applied over a glass slide to stick the sample. About 100 mg of sample was sprinkled over it to make a layer having a thickness of ̴ 0.5 mm. All the experiments were performed on an X-ray diffractometer (Philips X’Pert MPD, Eindhoven, Netherlands) having a sensitivity of 0.1 mg. The sample slide was placed vertically at an angle of zero degree in the sample chamber. An X-ray beam (Philip Cu target x-all ray tube) of 2kW was allowed to fall over the sample. As the slide moves at an angle of theta degree, a proportional detector detects diffracted X-ray at angle of 2-theta degrees. XRD patterns for poloxamer-188 soliddispersion were recorded using Philips JPCD software for powder diffractometry.
At present approximately 40% of new chemical entities identified by pharmaceutical companies are poorly water soluble. The formulations of poorly water soluble drugs (BCS) Class II for oral delivery presents a greatest challenge to the formulation scientists. Oral bioavailability depends on its solubility and dissolution rate. Several techniques have been developed over the years to enhance the dissolution of the drug such as soliddispersion, micronization, solubilization, and complexation with polymers, salt formation using prodrugs and adding surfactant. In present study the attempts have been made to increase the dissolution of BCS class II drug
Nifedipine release from soliddispersion formulations were studied in phosphate buffer solution, pH 7.4 (Simulated intestinal fluid) for 60 min. The results revealed that Nifedipine solubility rate was increased in soliddispersion formulations. Drug release varied with varying proportion of carrier. Soliddispersion of Nifedipine in 1:2 ratio showed greater drug release than 1:1 ratio. This may be due to increased carrier content. A rapid drug release was observed in Soliddispersion formulations prepared using PEG6000 compared to Urea as carrier. After 1 hour of dissolution, pure drug powder released only 44.1% nifedipine, whereas 83.7%, 90.9%, 62.1% and 72.9% drug were released from formulations F 1, F 2, F 3, and
Solid dispersions have attracted considerable interest as an efficient means of improving the dissolution rate and hence bioavailability of a range of hydrotrophic drugs. Up to 40% of new chemical entities discovered by the pharmaceutical industry today are poorly soluble or lipophilic compounds. Solid dispersions of poorly water-soluble drugs with water-soluble carriers reduce the incidence of these problems and enhanced dissolution. Soliddispersion is one of the most promising approaches for solubility enhancement. The term soliddispersion refers to a group of solid products consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug. The matrix can be either crystalline or amorphous. As per biopharmaceutical classification system class II drugs are with low solubility and high permeability and are the promising candidates for improvement of bioavailability by soliddispersion. Some of the practical aspects to be considered for the preparation of solid dispersions, such as selection of carrier, molecular arrangement of drugs in solid dispersions are discussed in this article. This article reviews the various preparation techniques for soliddispersion, characterization and compiles some of the recent technology transfers. Availability of a wide variety of polymers that are themselves poorly soluble or which swell under aqueous conditions suggests that solid dispersions have tremendous potential in the area of controlled release dosage forms.
or may not be changed, while those of the solute component disappear. The diffraction method is also particularly valuable in detecting compound or complex formation since its spectra or lattice parameters are markedly different from those of pure components. It has been used to disprove the existence of a patented salt formation between penicillin V and tetracycline 68 . The biggest drawback of using the diffraction method to study dispersion systems is its frequent inability to differentiate amorphous precipitation from molecular dispersion if the lattice parameter of the solvent component is not changed. This is because of the disappearance of the diffraction peaks or lines of the crystalline solute compound in both systems. This problem is encountered in the lower concentrations of drugs dispersed in polyethylene glycol 41 or polyvinylpyrrolidone polymers. The solidified eutectic of sulfathiazole-urea has a broad (instead of sharp melting point as found for its physical mixture) and lower melting range. This is attributed to the presence of amorphous sulfathiazole. The amorphous form is transformed into a crystalline form after annealing at high temperature, as shown by the appearance of its sharp diffraction peaks. The diffraction method has been used to study quantitatively the concentration of a crystalline component in the mixture 68, 69 . The ability of this method to quantitate the crystalline component in soliddispersion systems may be limited by its low concentration or weak intrinsic intensity of diffraction. The height of diffraction peaks may be attenuated by a reduction of crystallite size, usually below 0.2 µ. This is also accompanied by a broadening of the peaks 68 . An extremely fine crystalline dispersion of
The term soliddispersion refers to a group of solid products consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug. The matrix can be either crystalline or amorphous. The drug can be dispersed molecularly, in amorphous particles (clusters) or in crystalline particles 1 . Molecular dispersion of drug in polymeric carriers may lead to particle size reduction and surface area enhancement, which results improved dissolution rates. This technique is one of the oldest and most efficient method of enhancing the solubility and bioavailability of poorly water soluble drugs. Soliddispersion technology affects both specific surface area and solubility.
Recent Advances: As we know that soliddispersion technology has tremendous potential for increasing the bioavailability of drug, Successful development has been possible in recent years due to availability of few surface-active and self- emulsifying carriers with relatively low melting points and because of easy manufacturing process filling of drug along with carrier into hard gelatin capsules. Also, the technology has also step in developing controlled release preparations of poorly water soluble drugs.
Solid dispersions have engrossed substantial attention as an effectual means of refining the dissolution rate and hence the bioavailability of a variety of hydrophobic drugs. In this review, it is intended to discuss the future prospects related to the area of soliddispersion manufacturing. Improving oral bioavailability of drugs those given as solid dosage forms remains a challenge for the formulation scientists due to solubility problems. The dissolution rate could be the rate-limiting process in the absorption of a drug from a solid dosage form of relatively insoluble drugs. Therefore, increase in dissolution of poorly soluble drugs by soliddispersion technique presents a challenge to the formulation scientists. Soliddispersion techniques have attracted considerable interest of improving the dissolution rate of highly lipophilic drugs thereby improving their bioavailability by reducing drug particle size, improving wettability and forming amorphous particles. This review article discusses the various preparation techniques and characterization for soliddispersion and compiles some of the recent technology transfers in the form of patents.
4. Supercritical Fluid (SCF) Method:-Supercritical fluid methods are mostly applied with carbon dioxide (CO2), which is used as either a solvent for drug and matrix or as an anti-solvent. This technique consists of dissolving the drug and the carrier in a common solvent that is introduced into a particle formation vessel through a nozzle, simultaneously with supercritical CO2 (the gas is heated beyond its critical temperature and pressure). When the solution is sprayed, the solvent is rapidly extracted by the SCF, resulting in the precipitation of soliddispersion particles on the walls and bottom of the vessel. Advantages of this technique include reduction of particle size and residual solvent content as well as the high yield. 
Preparation of pellets by orifice ionic gelation technique: Method used for preparation of pellets was orifice ionic gelation technique in which 5% sodium alginate solution was prepared in 50 ml water and 2% soliddispersion was added to the solution, then, separately prepared 10% calcium chloride solution (100 ml). To this solution added dispersed solution drop by drop by continuous stirring at less than 300 rpm. They are then oven dried for 6 hr at 60°C
Surface soliddispersion technique was successful in improving the dissolution rate of poorly water-soluble drug Domperidone. SSDs of drug with Florite R as carrier showed significantly higher dissolution rate as compared to pure drug. The nature and amount of carrier used played an important role in the enhancement of dissolution rate. FTIR and DSC studies showed no evidence of interaction between the drug and carrier. XRD studies revealed that there is a change in crystallinity of drug to amorphous form. SSD tablets prepared with Florite R as carrier showed an enhancement of dissolution rate of drug as compared to marketed tablets. Mathematical modeling of drug release data fitted into first order kinetics. Accelerated stability studies indicated that there was no significant change in the drug content and % drug release.
water-soluble drugs overcame the limitations of previous approaches such as salt formation, solubilization by co- solvents, and particle size reduction. In case of soliddispersion drug disperse in the matrix generally a hydrophilic matrix and a hydrophobic drug, thereby forming a soliddispersion. When the soliddispersion is exposed to aqueous media, the carrier dissolves and the drug releases as fine colloidal particles. The resulting enhanced surface area produces higher dissolution rate and bioavailability of poorly water-soluble drugs 1, 2 . There are various types of polymers, solvent used in formulations. List of commonly used ones are given in table 1 & 2 and the list of poorly soluble drug used with which carriers is given in table 3.