It is suggested here that liquisolid technique has the potential to be optimized for the reduction of drug dissolution rate and thereby production of sustained release systems. In the present study, propranolol hydrochloride was dispersed in polysorbate 80 as the liquid vehicle. Then a binary mixture of carrier-coating materials Eudragit RL or RS as the carrier and silica as the coating material was added to the liquid medication under continuous mixing in a mortar. The final mixture was compressed using the manual tableting machine.
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Bioavailability depends on solubility of drug. Solubility is major challenge for the pharmaceutical industry with the developments of new pharmaceutical products. There are several approaches for solubility enhancement which includes micronization, Nanonisation, use of salt forms, use of surfactant, solid dispersion, and supercritical fluid recrystalization etc. Liquisolid technique is novel and efficient approach for solubility enhancement.
According to this method the conversion of water insoluble drug into dry looking, non adherent, free flowing and acceptably compressible powder by incorporating into suitable non volatile solvents, carrier material and coating materials. This free flowing powder is than subjected to Preformulation studies like Fourier transformed infrared spectroscopy, differential scanning Calorimetry for compatibility studies , angle of slide, flow properties, solubility studies, calculation of liquid load retention potential, liquid load factor etc.
These free flowing powders are subjected to compression for tablet or filled in capsules. The mechanism for solubility enhancement includes increase in wettability and surface of drug available for dissolution.
This method is efficient, economic, viable for industrial production, also useful in control drug delivery system. Hence due to above reasons liquisolid technique is most efficient and novel approach for solubility enhancement.
When oral route for administration of the drug is chosen then that drug should be sufficiently dissolved in gastric fluids for its proper absorption. If the drugs have less solubility in the gastric fluids then it will be less available for its absorption and due to this its bioavailability will be less.
Thus, one of the greatest challenges the pharmaceutical industries faces today is the application of technological strategies towards improving the dissolution performance of drugs, producing formulations with adequate bioavailability and therapeutic effectiveness. Several methods are studied for increasing dissolution performance and bioavailability including micronization, Nanonisation, complexation with cyclodextrins, solid dispersion, self emulsifying system, liquisolid systems etc.
Various methods used for enhancing solubility and thus bioavailability of drug are: 2, 3. Liquisolid technique: A liquisolid system refers to formulations formed by conversion of liquid drugs, drug suspensions or drug solution in non-volatile solvents, into dry, non-adherent, free flowing and compressible powder mixtures by blending the suspension or solution with selected carriers and coating materials.
Need of liquisolid technique: The oral route remains the preferred route of drug administration due to its convenience, good patient compliance and low medicine production costs. In order for a drug to be absorbed into the systemic circulation following oral administration, the drug must be dissolved in the gastric fluids.
Several studies have been carried out to increase the dissolution rate of drugs by decreasing the particle size, by creating nanoparticles and microparticles.
However, the fine drug particles have high tendency to agglomerate due to Vander Waals attraction or hydrophobicity, which both result in a decrease in surface area over time. Another way of increasing the dissolution rate is adsorption of the drug onto a high-surface area carrier. In this technique, the drug is dissolved in an organic solvent followed by soaking of the solution by a high surface area carrier such as silica.
Here, agglomeration of the drug particles is prevented due to the binding of drug to the carrier. However, due to the presence of the residual solvent in the drug formulation, it is disadvantageous to use toxic solvents. Concept of liquisolid technique: When the drug dissolved in the liquid vehicle is incorporated into a carrier material which has a porous surface and closely matted fibres in its interior as cellulose, both absorption and adsorption take place; i.
Then, the coating material having high adsorptive properties and large specific surface area gives the liquisolid system the desirable flow characteristics. Mechanism of enhancement of solubility: 1, 15 The wettability of the compacts in the dissolution media is one of the proposed mechanisms for explaining the enhanced dissolution rate from the liquisolid compacts.
Non-volatile solvent present in the liquisolid system facilitates wetting of drug particles by decreasing interfacial tension between dissolution medium and tablet surface. Thus, due to substantial increase in wettability and effective surface area for dissolution, liquisolid compacts may be expected to reveal enhanced release profiles of water-insoluble drugs.
Since dissolution of a non-polar drug is often the rate limiting step in gastrointestinal absorption, better bioavailability of an orally administered water-insoluble drug is achieved when the drug is already in solution, thereby displaying enhanced dissolution rates.
However, the drug release profile entirely depends on the characteristics of drug, carrier and vehicle used. Thus by altering these variables, liquisolid technique can be used for enhancing or retarding the drug release. Drug candidate: Mainly liquisolid technique is used for drug candidates comes under class II and class IV drugs. These drugs has low solubility and low dissolution rate. By using liquisolid technology dissolution rate of such poorly soluble drugs get improved by improving their solubility.
Carrier materials: Carrier materials should be sufficiently porous so that can enhance absorption properties and hence can absorb liquid sufficiently to enhance the solubility. Disintegrant: Mainly superdisintegrants increases rate of drug release, its wettability and increases solubility of drug particles within short period of time. Coating material: Coating material should be with high adsorptive property so that when used for coating the carrier particles can absorb the excessive non volatile solvent layer over the carrier particles and can give dry solid appearance to the saturated carrier particles having liquid external layer of non volatile solvent.
Hence can give dry, non adherent, free flowing powder particles. Formulation of liquisolid compacts: It is one of the novel techniques which is used for solubility enhancement and bioavailability of poorly water soluble drug.
It is first described by Spires. Flow behavior: 8 The flowability of a powder is of critical importance in the production of pharmaceutical dosage forms in order to reduce high dose variations. Angle of repose: The angle of repose physical mixtures of liquisolid compacts were determined by fixed funnel method. The accurately weighed physical mixtures of liquisolid compacts were taken in a funnel.
The height of the funnel was adjusted in such a way that the tip of the funnel just touches the apex of the heap of the powder. The powder was allowed to flow through the funnel freely into the surface.
The height and diameter of the powder cone was measured and angle of repose was calculated. Bulk Density: The loose bulk density and tapped density were determined by using bulk density apparatus apparent bulk density was determined by pouring the blend into a graduated cylinder. The bulk volume Vb and weight of the powder M was determined. The bulk density was calculated using the formula:. Tapped Density: The measuring cylinder containing a known mass of blend was tapped for a fixed time.
The minimum volume Vt occupied in the cylinder and the weight M of the blend was measured. The tapped density was calculated using the. It is calculated by the following formula. With this technology liquids such as solutions or suspensions of poorly soluble drugs in a non-volatile liquid vehicle are converted into acceptably flowing and compressible powders by simple physical blending with selected excipients named the carrier and the coating material.
As highest drug release rates are observed with liquisolid compacts containing a drug solution as liquid portion, liquisolid compacts may be optimized by selection of the liquid vehicle and the carrier and coating materials. The addition of Disintegrant may further accelerate drug release from liquisolid compacts.
The liquisolid technology may also be used for the preparation of sustained release formulations with zero order release pattern. Thus, a constant plasma level will be reached, which is maintained throughout the dosing interval.
For sustained release liquisolid compacts, the selection and the concentration of the excipients such as liquid vehicle, retarding agent matrix forming material as well as carrier and coating material play an important role.
The liquisolid approach is a promising technology because of the simple manufacturing process, low production costs and the possibility of industrial manufacture due to the good flow and compaction properties of liquisolid formulation. Int J Pharm Sci Res ; 8 7 : Article Information Sr No: 4. Download: Cited By: 6. Authors: Anand D. Savkare, Malavi R. Gholap and Pooja M. DOI: Various methods used for enhancing solubility and thus bioavailability of drug are: 2, 3 Micronization: This process involves reducing the size of the drug particles to 1 to 10 microns commonly by spray drying or by use of air attrition methods fluid energy or jet mill.
The process is also called as micro milling. Nanonisation: It is the process in which drug powder is converted in to nanocrystals of sizes nm.
There are three basic technologies currently in use to prepare nanoparticles. Pearl milling Homogenisation in water wet milling as in a colloid mill Homogenisation in non aqueous media Use of surfactants: Surfactants are very useful as absorption enhancers and enhance both dissolution rate as well as permeability of drug. They enhance dissolution rate primarily by promoting wetting and penetration of dissolution fluid into the solid drug particles.
Use of salt forms: Salts have improved solubility and dissolution as compared to the original drug. Alkali metal salts of acidic drugs like penicillin and strong acid salts of basic drugs like atropine are more water soluble than parent drugs. Supercritical fluid recrystalization: Supercritical fluids e. At near critical temperature, SCFs are highly compressible allowing moderate changes in pressure to greatly alter the density and mass transport characteristics of a fluid that determines its solvent power.
Once drug particles solubilised in SCFs, they may be greatly recrystallised at greatly reduced particle sizes. Solid dispersion: These are generally prepared by solvent or co precipitation method whereby both the guest solute and carrier solvent are dissolved in common volatile solvent system such as alcohol. The liquid solvent is removed by evaporation under reduced pressure or by freeze drying which result in amorphous precipitation of guest in a crystalline carrier.
Complex with cyclodextrins: The beta and gamma cyclodextrins and their several derivatives have unique ability to form molecular inclusion complexes with hydrophobic drugs having poor aqueous solubility.
Use of Amorphous, Anhydrates, Solvates and Metastable Polymorphs: Depending upon internal structure of solid drugs, selection of proper form of drug is with greater solubility is important.
In general amorphous are more soluble than metastable polymorphs, anhydrates are more soluble than hydrates and solvates are more soluble than non-solvates.
Can be applied to formulate liquid medication such as oily liquid drugs. Better availability of an orally administered water insoluble drug. Lower production cost than that of soft gelatin capsules. Production of liquisolid system is similar to that of conventional tablets. Viability of industrial production. Can be used for formulation of liquid oily drugs. Exhibits enhanced in-vitro drug release as compared to commercial counterparts, including soft gelatin capsule preparations.
Can be used in controlled drug delivery. Optimized sustained release, liquisolid tablets or capsules of water insoluble drugs demonstrate constant dissolution rates zero order release. Drug can be molecularly dispersed in the formulation. Demerits of liquisolid techniques: 9 Formulation of high dose lipophilic drugs the liquisolid tablet is one of the limitations of this technique. In order to achieve acceptable flowability and compactability for liquisolid powder formulation, high levels of carrier material and coating materials should be added.
This will increase the weight o tablets to above one gram which makes them difficult to swallow. Classification of liquisolid techniques: 15 Based upon liquid medication used: Powdered drug suspension.
The present work was aimed at enhancing the dissolution rate of olanzapine, an antipsychotic agent using the liquisolid technique. Liquisolid system is an innovative technique used for enhancing dissolution rate and bioavailability of poorly soluble drugs. A mathematical model was utilized to formulate liquisolid tablets. Two non-volatile liquids were used in the design of liquisolid tablets, Tween 80 and propylene glycol. The effect of formulation parameters, such as drug:non-volatile liquid ratio and carrier:coating ratio were observed.
The Liquisolid technique: an overview. A novel "Powder Solution Technology" involves absorption and adsorption efficiency which makes use of liquid medications, drug suspensions admixed with suitable carriers, coating materials and formulated into free flowing, dry looking, non adherent and compressible powder forms. Due to their significantly improved wetting properties a greater drug surface area is exposed to the dissolution media, resulting in an increased dissolution rate and bio availability. By using the Liquisolid technique, sustained drug delivery systems were developed for the water soluble drugs in which hydrophobic non-volatile solvents are used as vehicles. Uniterms: Liquisolid. Flow properties.