In contrast, the Dissocubes® technology employs piston-gap homogenizers. The technology was developed by Müller and colleagues (, ) and later. DissoCubes are part of Nanosuspension preparation. In which piston–gap high- pressure homogenization occurs. The main advantages of this technology. Employing piston-gap homogenizers, Müller and coworkers developed the Dissocubes technology (now belonging to Skyepharma plc) and the.
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One of the major problems associated with techmology soluble drugs is very low bioavailability. The problem is even more complex for drugs like itraconazole, simvastatin, and carbamazepine which are poorly soluble in both aqueous and nonaqueous media, belonging to BCS class II as classified by biopharmaceutical classification system.
Formulation as nanosuspension is an attractive and promising alternative to solve these problems. Nanosuspension consists of the pure poorly water-soluble drug technologt any matrix material suspended in dispersion. Preparation of nanosuspension is simple and technoloogy to all drugs which are water insoluble. A nanosuspension not only solves the problems of poor solubility and bioavailability, but also alters the pharmacokinetics of drug and thus improves drug safety and efficacy.
This review article describes the preparation methods, characterization, and applications of the nanosuspension. A range tecbnology parameters like solubility, stability at room temperature, compatibility with solvent, excipient, and photostability play a critical role in the successful formulation of drugs.
The conventional approaches include micronization, use of fatty solutions, use of penetration enhancer or cosolvents, surfactant dispersion method, salt formation, precipitation, etc. Additional approaches are vesicular system like liposomes, dispersion of solids, emulsion and microemulsion methods, and inclusion complexes with cyclodextrins, which show beneficial effect as drug delivery system but major problems of these techniques are lack of universal applicability dlssocubes all drugs.
Nanotechnology is defined as the science and engineering carried out in the nanoscale that is 10 —9 m.
As a result of increased solubility, the rate of flooding of the active compound increases and the maximum plasma level is reached faster.
This approach is useful for molecules with poor solubility, poor permeability, or both, which teechnology a significant challenge for the formulators. The reduced particle size renders the possibility of intravenous administration of poorly soluble drugs without any blockade of the blood capillaries.
The suspensions can also be lyophilized and into a solid matrix. Apart from these advantages, it also has the advantages of liquid formulations over others.
The principles of these methods are described dissoucbes detail and their merits and demerits are shown in Table 1. Precipitation method is a general method used to prepare submicron particles of poorly soluble trchnology. Rapid addition of solution to such solvent generally water leads to rapid supersaturation of drug in the solution, and formation of ultrafine amorphous or crystalline drug. This method involves nuclei formation and crystal growth which are mainly dependent on temperature.
High nucleation rate and low crystal growth rate are primary requirements for preparing a stable suspension with minimum particle size. This technique involve the following three steps: First, drug powders are dispersed in a stabilizer solution to form presuspension; after that, presuspension is homogenized by high pressure homogenizer at a low pressure sometimes for premilling; and finally homogenized at a high pressure for 10 to 25 cycles until the nanosuspensions are formed with desired size.
Dissocubes technology was developed by Muller in The instrument can be operated dissocubed pressure varying from to 1 bars 2 — 21 psi and up to 2 bars with volume capacity of 40 ml for laboratory scale.
For preparation techbology nanosuspension, technolpgy is essential to prepare a presuspension of the micronized drug in a surfactant solution using high-speed stirrer. According to Bernoulli’s Law, the flow volume of liquid in a closed system per cross section is constant. Due to this, water starts boiling at room temperature and forms gas bubbles, which implode when the suspension leaves the gap called cavitation and normal air pressure is reached. The size of the drug disssocubes that can be achieved mainly depends on factors like temperature, number of homogenization cycles, and power density of homogenizer and homogenization pressure.
Preprocessing like micronization of drug and high-cost instruments increases the overall cost of dosage form. Nanopure is suspension homogenized in water-free medium.
Because of very high boiling point and low vapor pressure of water, oils, and fatty acids, the drop of static pressure is not enough to begin cavitation in nanopure technology. Effect of impaction between the milling media and drugs gives essential energy for disintegration of the microparticulate system into nanoparticles.
In this process, the chamber of milling is charged with the milling media involving drug, stabilizer, and water or suitable buffer, which is rotated at a very high shear rate to generate suspension. Residues left behind in the finished product is a major problem of this method. Since many years, nanosuspensions are prepared through wet grinding processes by using pearl ball mill.
Nowadays, nanosuspensions can be prepared by dry milling methods. Stable nanosuspensions are prepared by using dry grinding of poorly soluble drug with soluble polymers and copolymers after dispersing in liquid medium. Nanosuspensions are also obtained by just diluting the emulsion, formed by using a partially water-miscible solvent as the dispersed phase. The emulsion technique is applicable for drugs which are either partially water miscible or soluble in volatile organic solvents.
Additionally, microemulsion templates can also produce nanosuspensions. Microemulsions are dispersions of two immiscible liquids like water and oil and stabilized thermodynamically by surfactant or cosurfactant. The drug is either loaded into preformed or internal phase of microemulsion and can be saturated by intimate mixing of drugs.
Nanosuspension: An approach to enhance solubility of drugs
Nanoedge is a combination of microprecipitation and high-pressure homogenization techniques. Solid lipid nanoparticles are mainly prepared by melt disxocubes method. Kipp and co workers firstly prepare nanosuspensions of ibuprofen by using melt emulsification method.
It is a dissofubes procedure. Drug is first added to tcehnology solution having stabilizer. The solution is heated at temperature higher than the melting point of the rissocubes and then homogenized by high-speed homogenizer for the formation of emulsion.
The temperature is maintained above the melting point of the drug during overall process. Finally, the emulsion is cooled to precipitate the particles. The particle size of nanosuspension mainly depends on parameters like drug concentration, concentration and type of stabilizers used, cooling temperature, and homogenization process.
This technique is also called opposite stream technology, uses a chamber where a stream of suspension is divided into two or more parts.
Both streams are colloid with each other at high pressure. The high shear force produced during the process results in particle size reduction. Dearns had prepared nanosuspensions of atovaquone using the microfluidization process. The major disadvantage of this technique is the high number of passes through the microfluidizer and that the product obtained contains a relatively larger fraction of microparticles. Various methods like techbology expansion of supercritical solution RESS disdocubes, supercritical antisolvent process, and precipitation with compressed antisolvent PCA process are used to produce nanoparticles.
In RESS technique, drug solution is expanded through a nozzle into supercritical fluid, resulting in precipitation of the drug as fine particles by loss of solvent power of the supercritical fluid. As the removal of solvent occurs, the solution gets supersaturated and finally precipitation occurs. In supercritical antisolvent process, drug solution is injected into the supercritical fluid and the solvent gets extracted as well as the drug solution becomes supersaturated.
The particle size, particle size distribution, and zeta potential affect the safety, efficacy, and stability of nanodrug delivery systems technoloty well as dissolution performance is also altered by solid state of nanoparticles.
DissoCubes: A Novel Formulation to Enhance SolubilityPharma Research Library | Pharma Info Index
Thus, characterization of nanoparticles plays a great role in forecasting in vitro and in vivo performance of nanodrug delivery systems. In vivo pharmacokinetic performance and biological function of nanosuspension strongly depends on its particle size and distribution, particle charge zeta potentialcrystalline state, and particle morphology. The mean particle size and particle size distribution affects saturation solubility, dissolution rate, physical stability, and in vivo performance of nanosuspensions.
A PI value of 0. It also gives a volume size distribution and can be used to measure particles ranging from 0. It is more efficient and suitable than LD to quantify the contamination of nanosuspensions.
Polymorphic or morphological changes of nanosized particles can be checked by assessing the crystalline state and particle morphology.
Surface charge properties of the nanosuspensions are studied through zeta potential. The value of particle surface charge indicates the stability of nanosuspensions at the macroscopic level.
By using postproduction processing, nanosuspensions are prepared into various dosage forms. Nanosuspension increases dissolution rate and absorption of drug due to smaller particle size and larger surface area.
The available marketed drugs in the form of nanosuspensions along with their routes of administration are mentioned in Table 3.
Available marketed drugs in the form of nanosuspension with their route of administration. Poor solubility, incomplete dissolution, and insufficient efficacy are the major problem of oral drug administration. Due to smaller particle size and much larger surface to volume ratio, oral nanosuspensions are specially used to increase the absorption rate and bioavailability of poorly soluble drugs.
By using standard manufacturing techniques, drug nanosuspensions can be simply incorporated into various dosage forms like tablets, capsules, and fast melts.
Journal of Nanomaterials
The nanosuspension of Ketoprofen was successfully incorporated into pellets for the sustained release of drug over the period of 24 hours. The present approaches for parental delivery tehcnology micellar solutions, salt formation, solubilization using cosolvents, cyclodextrin complexation, and more recently vesicular systems such as liposomes and niosomes.
But these methods have limitations like solubilization capacity, dissocubrs acceptability, high manufacturing cost, etc. To solve the above problems, the nanosuspension technology is used. Nanosuspensions are administered through various parental routes such as intraarticular, intraperitoneal, intravenous, etc. Additionally, nanosuspensions increase the efficacy of parenterally administered drugs.
Paclitaxel nanosuspension was reported to have their superiority in reducing the median tumor burden. For pulmonary delivery, nanosuspensions can be nebulized through mechanical or ultrasonic nebulizers. Due to the presence of many small particles, all aerosol droplets contain drug nanoparticles. Budesonide corticosteroid has been successfully prepared in the form of nanosuspension for pulmonary delivery. Different types of nebulizers are available for the administration of liquid formulations.
Some of the drugs successfully tried with pulmonary route are budesonide, ketotifen, ibuprofen, indomethacin, nifedipine, itraconazole, interleukin-2, p53 gene, leuprolide, doxorubicin, etc. Nanosuspensions are used in ocular delivery of the drugs for sustained release. Liang and co-workers prepared cloricromene nanosuspension for ocular delivery using Eudragit. Experiment showed technolog availability of drug in aqueous humor of rabbit eye.
Thus, nanosuspension formulation offers a promising way of improving the shelf-life and bioavailability of drug after ophthalmic application. Nanosuspensions are suitable for targeting particular organs because of their surface properties. Along with this, it is easy to alter in vivo behavior by changing the stabilizer. The drug will be taken up by the mononuclear phagocytic system which allows region-specific delivery.
This can be used for targeting antifungal, antimycobacterial, or antileishmanial drugs to macrophages if the pathogens persist intracellularly. He stated that the drug in the form of nanosuspension had EC 50 of 0.