Shenyang Pharmaceutical University, No. Production and hosting by Elsevier B. Graphical Abstract Keywords: Liquisolid technique, Dissolution enhancement, Poorly water-soluble drugs, Sustained release, pH variation, Photostability Abstract Most of the newly developed drug candidates are lipophilic and poorly water-soluble. Enhancing the dissolution and bioavailability of these drugs is a major challenge for the pharmaceutical industry.
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It should have high boiling point. It should be preferably water miscible. It should not be highly viscous organic solvent system. It should be compatible with having ability to solubilise the drug. The non volatile solvents used in the liquisolid system mainly acts as binding agent. 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: It is mainly divided into two categories: Preformulation studies Formulation of liquisolid compacts.
Preformulation studies: Solubility of drug: It is carried out by preparing saturated solution of drug in different solvents. This saturated solution is prepared by adding excess amount of drug in non solvent. This solution is shaken with shaker for specific period of time than it is filtered and analyzed under UV spectrophotometer. Determination of angle of slide: Angle of slide is used as a measure of the flow properties of powders.
Determination of angle of slide is done by weighing the required amount of carrier material and placed at one end of a metal plate with a polished surface. The end is gradually raised till the plate becomes angular to the horizontal at which powder is about to slide. This angle is known as angle of slide. Such liquid medication is added to the carrier coating material admixture and blended. Using equation 2 drug loading factors are determined and used for calculating the amounts of carrier and coating materials in each formulation.
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. In this step suitable carrier material with other excipients are added into initial mixture of drug and non volatile solvent. During this continuous mixing in the mortar should be going on. In the third step suitable superdisintegrants like sodium starch Glycolate or Crosspovidone is added in the prepared mixture with continuous shaking in a mortar.
In this step suitable coating material is added which adsorbs the layer of excess non volatile solvent over the carrier material. Due to this the liquid layer gets converted in the solid layer and this gives the dry, non adherent, free flowing powder particles.
The final mixture is then allowed to compress by using tablet compression machine. The prepared liquisolid tablet is then evaluated for its solubility, dissolution, compressibility FIG. 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. The bulk volume Vb and weight of the powder M was determined.
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. Precompression studies of the prepared liquisolid Powder systems: In order to ensure the suitability of the selected excipients, Fourier Transform Infra Red Spectroscopy, Differential scanning Calorimetry, X-ray Diffraction and Scanning Electron Microscope studies are to be performed.
In addition, flowability studies are also to be carried out to select the optimal formulae for compression, prior to the compression of the powders the dosage forms such as into tablets and capsules. Potassium bromide KBr pellet method is employed and background spectrum is collected under identical situation. Each spectrum is derived from single average scans collected in the region - cm-1 at spectral resolution of 2cm-2 and ratio against background interfereogram.
Spectra are analyzed by software. X-ray diffraction: For the characterization of crystalline state, X-ray diffraction XRD patterns are determined for physical mixture of drug and excipients used in formulation and for the prepared liquisolid compacts.
Absence of constructive specific peaks of the drug in the liquisolid compacts in X-ray diffractogram specify that drug has almost entirely converted from crystalline to amorphous or solubilised form. Such lack of crystallinity in the liquisolid system was understood to be as a result of drug solubilisation in the liquid vehicle i.
This amorphization or solubilization of drug in the liquisolid compacts it may contribute to the consequent improvement in the apparent solubility and enhancement of dissolution rate of the drug. Scanning electron microscopy: Scanning electron microscopy shows that there is presence or absence of crystal form of the drug or excipients in the formulation.
If SEM shows that there is absence of crystal form of the drug then it shows that now the drug is completely solubilised in to carrier system. After complete formulation liquisolid tablets also get evaluated for wt.
Contact angle measurement: For assessment of wettability, contact angle of liquisolid tablets is measured according to the imaging method. The commonly used method is to measure contact angle directly for a drop of liquid resting on a plane surface of the solid, the so-called imaging method.
A saturated solution of the drug in dissolution media is prepared and a drop of this solution is put on the surface of tablet. The contact angles are calculated by measuring height and diameter of sphere drop on the tablet.
Stability studies: In stability studies drug content is determined by charging up the crystals of the drug to accelerated stability conditions according to ICH guidelines Q1 R2. In this study samples are taken after each specific interval of the time.
These samples are then analyzed by using infra red spectrophotometer or differential scanning Calorimetry. During this study many researchers observed that if there is low drug concentration in liquid formulation then there is rapid drug release from the formulation. If In vitro release rates for liquisolid tablets are higher than the absorption rate will also be higher which enhances drug bioavailability.
In vivo study: This liquisolid technology is a promising tool for the enhancement of drug release of poorly soluble drugs. The absorption characteristics of Hydroclorothiazide liquisolid compacts in comparison with commercial tablets were studied in beagle dogs. Significant differences in the area under the plasma concentration time curve, the peak plasma concentration and the absolute bioavailability of the liquisolid and the commercial tablets were observed.
However, for the mean residence time, the mean absorption time, and the rate of absorption no significant differences were found. Estimation of drug content: The liquisolid compacts are powdered well and equivalent to 10mg of the drug powder is weighed and diluted using suitable solvent. The drug content is analyzed using UV-Visible spectrophotometer. It must: protect against all adverse external influences that can alter the properties of the product, g.
For liquisolid tablet: blister or strip package. For capsules: hard gelatin shell Storage: store at cool and dry place. Application: It is used for enhancing rate of dissolution of the many poorly soluble drugs by enhancing their solubility. Bioavailability of many class II and class IV drugs get enhanced by using liquisolid technique. Release rates of many poorly water soluble drugs get increased by using liquisolid system. It is also used for designing controlled drug delivery system.
Liquisolid technique is also successfully used for the formulation of many water insoluble or liquid lipophilic drugs. It is also used to formulate sustained release dosage form CONCLUSION: Various methods are studied to improve water solubility and drug release, among which the liquisolid technology is one of the most promising approaches.
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.
Beringhs, Humberto G. Ferraza,Marcos A. Segatto Silvac, Hellen K. The Theory and Practice of Industrial Pharmacy. Liquisolid systems and methods of preparing same. United State Patent, ; , International journal of Pharmaceutical Science and Research, ; 5 12 : In-vivo evaluation of hydrochlorothiazide liquisolid tablet in beagles dogs. International Journal of Pharmaceutical science.
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Liquisolid technique and its applications in pharmaceutics