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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However, the homogenization produced a narrowing of the particle size distribution, manifested through a decreasing polydispersity index. Both streams are colloid with each other at high pressure. This example of aprepitant demonstrates once again the importance of technolkgy increased bioavailability through nanonization.
Bioavailability is percentage of the drug which reaches the systemic circulation [ 3 ].
Nanosuspension: An approach to enhance solubility of drugs
Nanosuspension systems, Hamamatsu Nano technology. Liang and co-workers prepared cloricromene nanosuspension for ocular delivery using Eudragit. Atovaquone and buparvaquone for the treatment of leishmaniasis and opportunistic Pneumocystis carinii infections in HIV patients are effective in high doses due to low bioavailability.
However, in early stages, several in vivo studies clearly demonstrate the potential of these drug delivery vehicles in parenteral, oral, ocular, and pulmonary administration, where not only a controlled release but also tecunology appropriate bioadhesion is required.
The nanosuspension of Ketoprofen was successfully incorporated into pellets for the sustained release of drug over the period of 24 hours. A beagle dog model predicts improved bioavailability and diminished food effect on absorption in human.
Nanosuspension Technologies for Delivery of Poorly Soluble Drugs
The subsequent homogenization process improves the homogeneity of the nanosuspension by reducing the particle size and the amount of larger crystals.
The temperature is maintained above the melting point of the drug during overall process.
Products in pipeline In general, it can be stated that the advantages of the nanocrystal technology can be applied to many other poorly soluble drugs as well. This technique is also called opposite stream technology, uses a chamber where a stream of suspension is divided into two or more parts.
Nanosuspensions as particulate drug formulations in therapy: Advantages of pulmonary drug delivery over oral and parenteral drug administration include direct delivery dissodubes the site of action which leads to decreased dosage and side effects [ ].
Particles size of nanosuspensions critically determines the following characteristics of nanosuspensions [ 56 ]: This review presents the recent progress in therapeutic nanosuspensions produced by various techniques dissocuhes as high pressure homogenisation, media milling, and emulsification. PhD Thesis in preparation Kanellos M.
Another advantage of the annealing step is that it promotes the more stable crystalline form [ 37 ]. In this case, the improved reduction effectiveness was not linked to a change in the solid state behavior of the drug, but to the enhanced friability of the starting material [ 39 ].
Table 1 shows examples of drugs which belong to the different biopharmaceutical classes [ 3940 ]. Mixture of surfactants and polymers has been found to be beneficial for long-term stabilisation of nanosuspensions [ 78, ].
A bioavailability study comparing the peak plasma concentration and extent of absorption of Megace ES and megestrol acetate oral suspension revealed that in unfed patients, the bioavailability of Megace ES is minimally reduced while there was a substantial food effect for megestrol acetate oral suspension Femia Progress in high throughput screening methods leads to an even greater amount of newly discovered drugs that have poor water solubility.
However, these techniques have limitations in their particle size reduction performance, such as long production times and the necessity of employing a micronized drug as the starting material. In vivo studies of Wang et al. The objective of the annealing step is to improve the thermodynamic stability of the nanosuspensions by preventing the crystal growth of the precipitated particles to the micrometer range. Comminution Processes Top-Down 3.
This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3. The biochemical mechanism of progestin antitumor activity is not well known but may involve interaction with progester-one and glucocorticoid receptors, and androgenic properties.
In addition, incorporation of polymers on the particle surface and size reduction can be regarded as the future step in nanosuspension research. This destabilises the colloidal suspension. Plasma levels in fed and fasting condition are bioequivalent data on file, Abbott Labs.
PEG is commonly used to modify nanoparticle surface. Homogenization pressure, number of homogenization cycles, hardness of drugs, and temperature when thermosensitive drugs are processed are factors that influence the physical characteristics such as particle size of the resulting nanosuspensions. Next-generation technologies involve combinative particle size reduction methods to improve the particle size reduction effectiveness of the standard techniques [ 3 ]. Nanosuspension increases dissolution rate and absorption of drug due to smaller particle size and larger surface area.
To employ this combinative technique, the drug is dissolved in a suitable solvent liquid 1which is then mixed with an aqueous nonsolvent liquid 2. In the case of the WBM, the process time was reduced from technollogy hours to dixsocubes one hour to achieve a proper nanosuspension.
DissoCubes are crystalline nanoparticles of active substance obtained by a liquid state high energy process using a high pressure piston gap homogenizer to reduce the drug particle size djssocubes the presence of surface modifiers that associate at the freshly generated drug interface.
DissoCubes: A Novel Formulation to Enhance Solubility
Combinative Technologies In summary, the known limitations of the standard processes WBM, HPH for the production of drug nanocrystals are the necessity of a micronized drug as the starting material and the long runtimes for the top-down equipment [ 2 ]. Oral Drug Delivery Poor solubility, incomplete dissolution, and insufficient efficacy are the major problem of oral drug administration.
The plasma levels achieved by the antineoplastic drug nanocrystals were tested in animal models. All nanocrystals in the first four products were produced using the pearl mill technology by Elan Nanosystems. Media milling Liversidge et al. This production technique combines a microprecipitation step a solvent-antisolvent technique followed by a high-energy process. Used with permission from Junghanns One needs to bear in mind that these nanocrystals need to be stabilized in order not to grow to the micrometer range.
High pressure homogenization and wet bead milling are standard comminution techniques that have been already employed to successfully formulate poorly soluble drugs and bring them to market. However, limitations such as toxicity of surfactants which are often used in high doses to keep drug in the dispersed state and limited drug loading have been identified [ 24 ].