liquisolid compact technology


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OBJECTIVES To understand and explore concept of liquisolid compact technique. To study formulation aspects of liquisolid systems. To get overview of evaluation and pharmaceutical applications of liquisolid compacts. 3


CONTENTS Introduction Need of Liquisolid compact technique Formulation of liquisolid compacts Requirements for Liquisolid system New mathematical model to formulate liquisolid system Preformulation study Preparation of liquisolid system Evaluation Precompression evaluation Post compression evaluation Applications of liquisolid compacts Case study Conclusion References 4


INTRODUCTION According to spireas et al The term “ liquisolid compacts technique ” refers to process of preparation of immediate or sustained release tablets or capsules using the “liquisolid systems” combined with the inclusion of appropriate excipients required for tabletting or encapsulation, such as disintegrant for immediate release, binders for sustained release action. 5

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Historical development Developed from- Powdered drug solutions Powdered drug suspensions Powdered liquid drugs Poor , erratic flowability and compressibility Liquid squeezing out phenomenon and unacceptably soft tablets . Spireas and Bolton(1996) 6

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Advantages of Liquisolid compacts Low cost formulations. Production of them is similar to that of conventional tablets. Enhanced dissolution and bioavailability than conventional formulations . Excellent flowability and compressibility. Drug release can be modified using suitable formulation ingredients. Capability of industrial production. 7

Need of Liquisolid compact technique :

Need of Liquisolid compact technique For poorly soluble, insoluble,liquid drugs or lipophilic drug . For poorly flowable powder admixtures. To aid direct compression. To improve efficiency of tablet manufacturing. 8


FORMULATION Requirements for Preparation of Liquisolid Systems 9

Ideal Characteristics Of Components In Liquisolid Compact :

Ideal Characteristics Of Components In Liquisolid Compact 10

B. Mathematical model for designing the liquisolid systems:

B. Mathematical model for designing the liquisolid systems Excipients ratio R =Q/q Where, R represents the ratio between the weights of carrier (Q) and coating (q) materials. Liquid load factor (L f ) L f = W/Q Where, L f is ratio of the weight of liquid medication (W) over the weight of the carrier powder (Q) in the system,


Cont… 12 Maximum liquid load factors (  L f ) to produce acceptably flowing liquisolid systems L f =  +  (1/R) Maximum compressible liquid load factors(  L f ) required to produce liquisolid compacts with acceptable compaction properties  L f =  + ψ (1/R) Optimum liquid load factor, L f , required to produce simultaneously acceptably flowing and acceptably compressible liquisolid preparations is equal to : L f =  L f when  L f <  L f Or, L f =  L f when  L f <  L f

C. Pre-formulation Studies:

C. Pre-formulation Studies Solubility studies Determination of angle of slide Determination of flowable liquid retention potential (Φ value) Determination of Φ L f of each powder system Graph of Φ L f vs 1/R 4. Calculation of liquid load factor (L f ) L f = W/Q 13


Cont… 5. Liquisolid compressibility test (LSC) Determination of crushing strength (S) Determination of pacticity ( Ω ) Graph of log Ω vs C w Calculation of ψ Determination of  L f Graph of  L f vs 1/R 6. DSC of drug 7. XRD of drug 8. SEM of drug 14

D. Steps involved in preparation of liquisolid compacts:

D. Steps involved in preparation of liquisolid compacts Wet particles Nonvolatile solvent system Or Final formulation Tabletting or encapsulation Liquid medication Drug solution or drug suspension Liquid drug Carrier material Coating material Solid drug Liquisolid systems 15


EVALUATION Precompression Evaluation (Evaluation Of Liquisolid System) Flow properties Angle of repose Fixed Funnel Method. II. Carr’s index tan  = h/r Sr .No. Angle of repose (degrees) Type of flow 1 < 20 Excellent 2 20-30 Good 3 30-34 Passable 4 > 40 Very poor Sr .No. Carr’s index (%) Type of flow 1 5-15 Excellent 2 12-16 Good 3 18-21 Fair to passable 4 23-35 Poor 5 33-38 Very poor 6 > 40 Extremely poor 16

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III. Hausner’s ratio >1.6 less free flowing powders <1.25 indicate good flow. 17

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2 . Post compression studies ( Evaluation of liquisolid compacts ) 18

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Sr. No. Average weight of tablet %deviation 1 80 mg or less  10 2 80 mg to 250 mg  7.5 3 250 mg or more than 250 mg  5 19


APPLICATIONS 1.Solubility and dissolution improvement Use of non-volatile solvent causes increased wettability and ensures molecular dispersion of poorly soluble, liquid, insoluble or lipophilic drug. drug. Transformation into an amorphous form having highest energy and solubility. 2.Flowability and compressibility Improvement Excipients possessing large surface areas, fine particle size and granular grades produce good flow and compression properties Drug existed in a molecular state of subdivision and systems are free flowing, non-adherent, dry looking powders. 20

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3.Bioavailability improvement Due to significantly increased wetting properties and surface of drug available for dissolution, liquisolid compacts display enhanced drug release properties, and consequently, improved bioavailability. 4.For designing of sustain release tablet Liquisolid technique can change the dissolution rate of drugs. If hydrophobic carriers such as Eudragit RL and RS are used, sustained release systems can be obtained. 21


CASE STUDY Atorvastatin Calcium 22 HMGCoA reductase inhibitor. BCS class II drug Liquisolid tablets containing 10 mg ATR Formulation -

X-ray powder diffraction (XRPD):

X-ray powder diffraction (XRPD) 23

Differential scanning calorimetry (DSC):

Differential scanning calorimetry (DSC) 24

In vitro performance:

In vitro performance 25

In vivo profile:

In vivo profile 26


CONCLUSION The Liquisolid technique is a promising alternative to enhance the absorption as well as dissolution rate their by it may enhance the bio availability of a poorly soluble, liquid drugs, insoluble or lipophilic drugs. Liquisolid tablets prepared were found superior in terms of faster disintegration time, superior dissolution profile, acceptable tablet properties and stability. The technique is also used to design immediate release or sustained release systems. Therefore, this technique has the potential as safer and efficacious method, hence should considered to be manufactured on a large scale. 27


REFERENCES Spiras S, Bolton SM, Liquisolid systems and methods for preparing same, United States patent 6,096,337, 2000. Fahmy RH, Kassem MA, Enhancement of famotidine dissolution rate through liquisolid tablet formulation: in vitro and in vivo evaluation, Eur J Pharm Biopharm, 2008; 69(3): 993-1003. Javadzadeh Y, Musaajrezaei , Nokhodchi A, liquisolid technique as a new approach to sustain propranolol hydrochloride release from tablet matrices , Int J Pharm,2008:1-7. Javadzadeh Y, Navimipour B, Nokhodchi A, Liquisolid technique for dissolution rate enhancement of a high dose water insoluble drug (carbamazepine), Int J Pharm, 2007:341:26-34. 28

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Mehta RM, Processing of tablets, Pharmaceutics-I, 4 th ed., vallabh prakashan, 2007, 238-267. Amidon GE, Physical and mechanical property characterization of powders, In: Brittain HG., Physical characterization of pharmaceutical solids, Drugs and pharmaceutical sciences, vol. 70, Marcel Dekker Inc., New York, 1995, P. 282– 317. Indian pharmacopoeia, Gov. of India, Ministry of health and family welfare, Delhi: controller of India: New Delhi, India, 2007; p 662-663, 1021-1022. Gubbi SR, Jarag R, Formulation and characterization of Atorvastatin calcium liquisolid compacts, Asian J Pharm Sci 2010, 5 (2): 50-60. 29

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Thank You… 30

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