Keywords: Liquisolid compacts, Mefenamic acid, Liquid retention potential (Ø), Avicel-PH 102, Aerosil 200, drug release kinetics.

Transcription

1 International Journal of Pharmaceutical Development & Technology e ISSN X Print ISSN FORMULATION AND EVALUATION OF MEFENAMIC ACID EXTENDED RELEASE LIQUISOLID TABLETS CH.Pradeep Kumar* 1, P.Venugopalaiah, CH. Praveen Kumar, K. Gnanaprakash, M. Gobinath 1 Department of Pharmaceutics, Ratnam Institute of Pharmacy, SPSR Nellore, Andhra Pradesh, India ABSTRACT Liquisolid system refers to formulations formed by conversion of liquid drugs, drug suspension or drug solution in nonvolatile solvents in to non-adherent, free flowing and compressible powder mixtures by blending the solution or suspension with selected carriers and coating materials. The aim of the present work was to formulate and evaluate extended liquisolid compacts of Mefenamic acid. Liquisolid extended formulations were prepared by using HPMC K100M as adjuvant for extended. Different liquisolid compacts were prepared using a mathematical model to calculate the required quantities of powder and liquid ingredients to produce acceptable and free flowing compressible mixtures. Avicel PH 102, Aerosil-200 were employed as carrier and coating materials. The prepared liquisolid compacts were evaluated for their flow properties such as bulk density, tapped density, angle of repose, Carr s compressibility index, Hausner s ratio. Drug-excipients interactions were studied by FT-IR. Drug rates of liquisolid compacts shows significant benefit and distinct profiles when compared to normal extended tablets and from the results it was concluded that at higher amount of Aerosil 200 (Batch F12), drug was found to be retarded as compared to other batches. Increase in concentration of HPMC K100M might be responsible to get extended effect. The obtained data of liquisolid compacts were fitted into several mathematical models such as Zero order, First order, Higuchi, Korsemayer-Peppas, and the obtained data was fitted into zero order pattern followed by non-fickian transport mechanism. Drug profiles on model fitting follow Peppas model as best fit model which indicates drug diffusion in hydrated matrix and polymer relaxation. Keywords: Liquisolid compacts, Mefenamic acid, Liquid retention potential (Ø), Avicel-PH 102, Aerosil 200, kinetics. INTRODUCTION The oral route is the preferred route for the chronic drug therapy. Numerous potent lipophilic drugs exhibit low oral bioavailability due to their poor aqueous solubility properties. Therapeutic effectiveness of a drug depends up on the bioavailability and ultimately upon the solubility and dissolution rate molecules. Solubility and dissolution rate are the important parameters to achieve desired concentration in systemic circulation for pharmaceutical response to be shown [1]. BCS class II drugs pose challenging problems in their pharmaceutical product development process because of their low solubility and dissolution rates. They require enhancement in solubility and dissolution rate in their formulation development especially solid dosage forms such as tablets and capsules. More recently, powdered solution (liquisolid) technology has been proposed as a technique for the delivery of water-soluble drugs. The concept of powdered solutions involves converting drug solutions or liquid drugs into a dry, non-adherent, free-flowing compressible powder by admixturing the liquid drugs or drug solutions with a selected carrier. Although the dosage form is a solid, the drug was held in a solubilized liquid state, which enhances diffusion directly into cells. Alternatively, improves the wetting properties of the drug and therefore enhanced dissolution [2]. Since drug dissolution is often the rate limiting step in gastrointestinal absorption, the significant increase in wetting properties and surface area particles available for dissolution from liquisolid compacts may be expected to display enhanced characteristics and, consequently, improved oral bioavailability. The technique of liquisolid compacts has been successfully employed to improve the In Vitro of poorly water soluble drugs such as Carvidilol [3], Corresponding Author :- CH.Pradeep Kumar - deepuu75@gmail.com 80 P a g e

2 Bromhexine Hydrochloride [4], Furosemide [5], carbamazepine [6], Fenifibrate [7], Indomethacin [8], Aceclofenac [9], ketoprofen [10], theophylline [11], propranolol hydrochloride [12], Lansoprazole [13], Irbesartan [14], Lornoxicam [15], simvastatin [16], tramadol hydrochloride [17], and fenofibrate [18]. Mefenamic acid is one of the Anthranilic acid derivatives of Non-Steroidal Anti-Inflammatory Drugs (NSAID). Recent clinical studies on Mefenamic acid revealed that the drug is an effective agent for accumulation and moderate to severe ulceration in GI tract. Repeated administration of high doses of mefenamic acid ( mg- 3 s/day) leads to accumulation in GIT causes Inflammatory bowel diseases, peptic ulcers, and also due to its sudden causes local irritation in the stomach which is a major limitation for mefenamic acid as conventional dosage form, and its less half-life period (< 2hrs). To reduce frequent administration of dosage form and to improve patient compliance extended liquisolid mefenamic acid formulation is desirable. Hence the main objective of this work was to retard/sustain the from the dosage form to eliminate the repeated administration and also to increase the half-life of mefenamic acid in GI environment. In the present study, Hydroxy Propyl Methyl Cellulose (HPMC) K100M was used as adjuvant for sustaining the from liquisolid compacts. Poly Ethylene Glycol (PEG-400) was used as non-volatile lipophilic solvent. Avicel PH 102 (Microcrystalline cellulose), Pregelatinized Starch and Aerosil 200 (Colloidal silicon dioxide) were used as carrier and coating materials, respectively. Precompression studies such as determination of angle of slide, Hausner s ratio, Carr s index and stereomicroscopic analysis was also studied. The discrimination of profiles was compared with normal extended tablets of Mefenamic acid (without liquid lipophilic solvent and Aerosil 200). Model fitting of the results was also done for different models such as Zero order, First order, Higuchi plot and Korsemayer-Peppas plot models. The formulation design of liquisolid systems was done in accordance with new mathematical model described by spireas et al., [19]. MATERIALS AND METHODS Materials Mefenamic acid was obtained from Alexo pharma (India). HPMC K100M, Avicel PH-102, Starch pregelatinized, Aerosil 200 were purchased from Drugs India Pvt ltd (India). Poly ethylene glycol 400 was obtained from Fischer scientific. All the ingredients and chemicals utilized were of analytical grade. Methods Application of mathematical model for design of Liquisolid compacts Before designing the liquisolid system, the preformulation studies should be performed first, includes Carrier-Coating material ratio (R) Determination of flowable liquid retention potential (Ø value) Calculation of liquid load factor (L f ) Liquid solid compressibility test (LSC) The flowability and compressibility of liquisolid compacts are addressed concurrently in the new formulation mathematical model of liquisolid systems, which was used to calculate the appropriate quantities of the carrier and coating materials required to produce acceptably flowing and compressible powders based on new fundamental powder properties called the flowable liquid retention potential (Ø value) and compressible liquid retention potential (Ψ value) of the consistent powders [20, 21]. Carrier-Coating material ratio (R) It is the ratio between the quantities of carrier (Q) and coating (q) present in the formulation. It is represented as R=Q/q Determination of flowable liquid retention potential (Ø) It is defined as maximum weight of liquid that can be retained per unit powder material in order to produce an acceptably flowing liquid/powder admixture. This Ø-value of powders may be determined using a new procedure, the liquisolid flowability (LSF) test. This test is basically a titration-like procedure in which grams of mixtures of the powders under investigation, with increasing amounts of a non-volatile solvent (i.e., liquid/solid weight composition), such as, for example, poly ethylene glycol, light mineral oil and clofibrate, are prepared using a standard mixing process which ensures uniformity, and their flow rate and consistency are assessed using a recording powder flow meter (RPF) [19, 22, 23]. Lf= Ø CA + Ø CO (1 / R) Where, Ø and Ø are the constant liquid retention potential values of carrier and coating materials, respectively. By calculating L f and W, we can calculate the Q and q required for liquisolid systems [24]. Calculation of liquid load factor (L f ) It is defined as ratio of weight of liquid medication (W) to weight of carrier material (Q). Different concentrations of nonvolatile solvents are taken and the drug is dissolved and the carrier coating material is added and blended. L f =W/Q Where W is ratio of weight of liquid medication and Q is weight of carrier material [25]. By use of above mathematical model, liquisolid compacts were formulated. Formulation of Mefenamic acid Liquisolid compacts Mefenamic acid liquisolid tablet preparation method involves, first a mathematically calculated amount of pure drug was weighed and dissolved in the suitable amount of lipophilic liquid vehicle in a molecularly 81 P a g e

3 dispersed state. For attaining good flow properties trial and error methods were used i.e. changing the carrier: coating ratio from 50:1 to 5:1 ratios according to new mathematical model expressions proposed by Liao [26]. This liquid medication is poured on the suitable amount of carrier material. The liquid medication is absorbed into the carrier internally and externally. Finally, coating material was added for dry looking, adherent to the carrier material for achieving good compression properties. Liquid medication is incorporated into carrier material which has a porous surface and closely matted fibers in its interior as cellulose [20]. Both absorption and adsorption takes place, i.e. the liquid absorbed into the interior of the particles is captured by its internal structure and after saturation of this process, adsorption of the liquid onto the internal and external surface of the porous carrier particles occurs. According to the above mathematical model calculated quantities of Mefenamic acid and propylene glycol 400 was accurately weighed in 20 ml glass beaker and then heated to 80 C. Resulting hot medication was incorporated into calculated quantities of carrier and coating materials. Mixing process is carried out in three steps as described by Spireas et al., During first stage, system was blended at an approximate mixing rate of one rotation per second for approximately one minute in order to evenly distribute liquid medication in the powder. In second stage, the liquid/powder admixture was evenly spread as a uniform layer on the surfaces of mortar and left standing for approximately 5 min to allow drug solution to be absorbed in the interior of powder particles. In third stage, powder was scraped off the mortar surfaces by means of aluminum spatula and then blended with HPMC K100M, for another 30 seconds in a similar to first stage. This gives final formulation of liquisolid tablets. Prepared liquisolid formulation was compressed by 16 station Rotary tablet punching machine (Cadmach). EVALUATION Standard graph for Mefenamic acid Step 1: Preparation of standard stock solution: An accurately weighed quantity of 100 mg of mefenamic acid was taken in a 100 ml standard flask. To this equal volume of 0.1N HCl was added and made up to the volume. Step 2: Preparation of sample solution: Different aliquots (0.0, 0.5, 1.0,, 5.5 ml) of Mefenamic acid solution were accurately measured from the above primary stock and transferred into a series of 100 ml volumetric flasks and volume made up to the mark with 0.1 M HCl. Then all dilutions were scanned by UV Spectrophotometer at 285nm against blank and the results were tabulated and a plot was drawn between concentration (µg/ml) on x-axis and absorbance (nm) over y-axis. Determination of Solubility of Mefenamic acid in various lipophilic solvents Saturated solutions were prepared by adding excess of Mefenamic acid to different lipophilic solvents includes Propylene glycol, PEG-400, Sorbitan esters ( Span-80, Span-60, Tween-80, Tween-60, Tween-20, Glycerin, SLS- 10%) and shaking on the shaker for 48 h at 25 C under constant vibrations. The solutions were filtered through a 0.40 micron filter, after this, the solutions are filtered, diluted and analyzed spectrophotometrically at 285 nm against blank sample (blank sample was solution containing same concentration of used without drug). Three determinations were carried out for each sample to calculate the solubility of Mefenamic acid. Drug-Excipient compatibility study: FT-IR spectroscopy FT-IR patterns were studied by Shimadzu 8400S, Japan FT-IR spectrometer. The samples (Mefenamic acid and Excipients) were previously ground and mixed thoroughly with potassium bromide, an infrared transparent matrix, at 1:5 (Sample: KBr) ratio, respectively. The KBr discs were prepared by compressing the powders at a pressure of 5 tons for 5 min in a hydraulic press. The scans were obtained at a resolution of 4 cm -1, from 4000 to 400 cm -1. Pre-compression evaluation studies Pre-formulation studies such as bulk density, tapped density, angle of repose, compressibility index, Hausner s ratio were performed for drug alone and liquisolid compressible powders as per the standard procedures and the results were tabulated in table-3 [27-29]. Post-compression evaluation parameters After compression of desired doses and its excipients into suitable tablet dosage form, each batch was subjected to the following evaluation parameters such as Weight variation, Friability, Tablet dimensions, Drug content analysis, Hardness and In-vitro studies according to the standard pharmacopoeial procedures [28, 29]. In-vitro dissolution studies The studies were done on eight station USP dissolution apparatus I (Lab India). All batches of tablets were evaluated using 900 ml of sequential gastrointestinal medium, i.e. 0.1N hydrochloric acid (ph 1.2) for first two hours, acetate buffer of ph 4.5 for next 2 hrs and then phosphate buffer of ph 7.4 for 8 hours. Temperature was maintained at 37 ± 0.5 C throughout the study and stirring at 50 rpm was carried out. Samples were collected periodically, filtered through 0.45 micron filter and replaced with fresh dissolution medium. After filtration Samples were properly diluted and Mefenamic acid concentrations were analyzed spectrophotometrically at 285 nm. The d at interval was calculated and plotted against. Mathematical modeling for profile 82 P a g e

4 The cumulative amount of Mefenamic acid d from the formulated tablets at different intervals were fitted in to several kinetic models such as Zero order kinetics, First order kinetics, Higuchi model and Korsemayer-peppas model to characterize mechanism of. Zero order kinetics It describes the system in which the rate is independent of its concentration. Q t = Q 0 +K 0 t Where, Q t = amount dissolved in t Q 0 = initial amount in the solution K 0 = Zero order constant If the zero order kinetic is obeyed, then a plot of Q t vs. t will give a straight line with a slope of K 0 and an intercept at zero. To study the kinetics, data obtained from in vitro studies were plotted as cumulative amount of d vs.. First order kinetics It describes the from the systems in which the rate is concentration dependent. Q t = Q 0 + K 1 t/2.303 Where, Q t = amount of in t Q 0 = initial amount in the solution K 1 = first order constant If the pattern follows first order kinetics, then a plot of log (Q 0- Q t ) versus t will be a straight line with a slope of K 1 /2.303 and an intercept at t=0 of log Q 0. The data obtained are plotted as vs.. Higuchi model It describes the fraction of from a matrix is proportional to square root of. Mt/Mα = K H t 1/2 Where, Mt & Mα = cumulative amounts of rug at t and infinite K H = Higuchi dissolution constant reflection formulation characteristics. If the Higuchi model of (i.e., Fickian diffusion) is obeyed, then a plot of Mt/Mα vs. t 1/2 will be a straight line with a slope of K H. The data obtained were plotted as cumulative vs. square root of. Korsemayer-Peppas model The power law describes that the fractional amount of is exponentially related to the and adequately describes the from slabs, cylinders and spheres. Mt/Mα = Kt n [Mt/Mα] = K + n log t Where, Mt & Mα = cumulative amounts of rug at t and infinite K = constant incorporating structural and geometrical characteristics of CR device n = diffusional exponent indicative of the mechanism of for drug dissolution. To study the kinetics, data obtained from in vitro studies were plotted as vs. log. Table1. Formulation composition of Mefenamic acid Liquisolid Extended tablets Formulation code Drug (mg) PEG-400 (mg) R L f Carrier material (mg) Coating material (mg) AEROSIL-200 F HPMC K100 (mg) Total weight (mg) F F F STARCH F F F F F F AVICEL F PH F ERT* *- Contains Talc & Magnesium stearate (30mg each) without PEG-400 & Aerosil-200 ERT- Normal Extended Release Tablets 83 P a g e

5 Table 2. Solubility results of Mefenamic acid in various solvents at 25 0 C SL.No Solvent / vehicle Solubility (mg/ml) 1 Water Ethanol Propylene glycol Glycerin Buffer S.L.S (10%) Tween Polyethylene glycol Table 3. Micromeritic parameters for mefenamic acid liquisolid powders Sl.No Bulk density Tapped density Angle of Repose (θ)* Carr s index (%)* Hausner s Ratio* Pure drug F ± ± ±0.01 F ± ± ±0.01 F ±o ± ±0.02 F ± ± ±0.01 F ± ± ±0.03 F ± ± ±0.01 F ± ± ±0.02 F ± ± ±0.01 F ± ± ±0.01 F ± ± ±0.01 F ± ± ±0.03 F ± ± ±0.01 ERT ± ± ±0.02 *Mean n=3 Table 4. Post compression parameters for Mefenamic acid Liquisolid tablets Tablet dimensions* Weight Hardness* Friability* SL.No Thickness Diameter variation* (mg) (Kg/Cm 2 ) Fines (%) (mm) (mm) F1 6.16± ± ± ± ±0.3 F2 6.37± ± ± ± ±0.5 F3 6.55± ± ± ± ±0.6 F4 6.61± ± ± ± ±0.1 F5 6.82± ± ± ± ±0.5 F6 7.00± ± ± ± ±0.4 F7 6.12± ± ± ± ±0.1 F8 6.17± ± ± ± ±0.7 F9 6.40± ± ± ± ±0.3 F ± ± ± ± ±0.2 F ± ± ± ± ±0.5 F ± ± ± ± ±0.2 ERT 5.85± ± ± ± ±0.4 *Mean n=3 Content uniformity* (%) Table 5. In-vitro data for Mefenamic acid Extended Liquisolid tablets (hrs) Dissolution medium F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11 F12 ERT o.o1 N HCl ph Phosphate P a g e

6 5 buffer ph phosphate buffer Table 6. In-vitro kinetics data for formulation F1 % , Table 7. In-vitro kinetics data for formulation F Table 8. In-vitro kinetics data for formulation F P a g e

7 Table 9. In-vitro kinetics data for formulation F Table 10. In-vitro kinetics data for formulation F Table-11. In-vitro kinetics data for formulation F Table 12. In-vitro kinetics data for formulation F P a g e

8 Table 13. In-vitro kinetics data for formulation F Table 14. In-vitro kinetics data for formulation F Table 15. In-vitro kinetics data for formulation F P a g e

9 Table 16. In-vitro kinetics data for formulation F Table 17. In-vitro kinetics data for formulation F Table 18. In-vitro kinetics data for ERT formulation Table 19. Parameters and determination coefficients of profile from Mefenamic acid extended liquisolid compacts (F1-F12) and extended tablet (ERT) Formulation Correlation Coefficient values (R 2 ) Diffusion Exponent value (n) code Zero First Higuchi Korsemayer-peppas order order F F P a g e

10 F F F F F F F F F F ERT Fig 1. Calibration curve for mefenamic acid at 285nm Fig 2. FT-IR Spectra of Mefenamic acid (pure drug) 89 P a g e

11 Fig 3. FT-IR Spectra of Mefenamic acid + Avicel PH Aerosil HPMC K100M Pradeep Kumar CH. et al. / IJPDT / 3 (2), 2013, Fig 4. FT-IR Spectra of Mefenamic acid + Starch + Aerosil HPMC K100M 90 P a g e

12 Fig 5. FT-IR Spectra of Physical mixture (Mefenamic acid + Avicel PH Starch + Aerosil HPMCK100M + Poly ethylene glycol-400) Fig 6. In-vitro kinetics data (Zero order plots) for formulation F1, F2, F3 91 P a g e

13 Fig 7. In-vitro kinetics data (Zero order plots) for formulation F4, F5, F6 Fig 8. In-vitro kinetics data (Zero order plots) for formulation F7, F8, F9 Fig 9. In-vitro kinetics data (Zero order plots) for formulation F10, F11, F12 Fig 10. In-vitro kinetics data (First order plots) for formulation F1, F2, F3 Fig 11. In-vitro kinetics data (First order plots) for formulation F4, F5, F6 Fig 12. In-vitro kinetics data (First order plots) for formulation F7, F8, F9 92 P a g e

14 Fig 13. In-vitro kinetics data (First order plots) for formulation F10, F11, F12 Fig 14. In-vitro kinetics data (Higuchi plots) for formulation F1, F2, F3 Fig 15. In-vitro kinetics data (Higuchi plots) for formulation F4, F5, F6 Fig 16. In-vitro kinetics data (Higuchi plots) for formulation F7, F8, F9 Fig 17. In-vitro kinetics data (Higuchi plots) for formulation F10, F11, F12 Fig 18. In-vitro kinetics data (Korsemayer- Peppas plots) for formulation F1, F2, F3 93 P a g e

15 Fig 19. In-vitro kinetics data (Korsemayer- Peppas plots) for formulation F4, F5, F6 Fig 20. In-vitro kinetics data (Korsemayer- Peppas plots) for formulation F7, F8, F9 Fig 21. In-vitro kinetics data (Korsemayer- Peppas plots) for formulation F10, F11, F12 Fig 22. Structure of mefenamic acid showing the group responsible for the COX inhibiting activity RESULTS Application of new mathematical model for design of liquisolid systems Mefenamic acid was selected as model drug for this study as a suitable candidate for extended. Liquisolid hypothesis of Spireas et al., states that drug candidate dissolved in liquid nonvolatile vehicle and incorporated into carrier material having porous structure and closely matted fibers in its interior, phenomenon of both adsorption and absorption occurs. This concludes that drug in the form of liquid medication is absorbed initially in the interior of particles of carrier and after saturation of this process it gets adsorbed into internal and external surfaces of carrier. Coating materials such as Aerosil 200 which have high adsorptivity and grater surface area lead the liquisolid systems desirable flow properties [15]. Mathematical model equation for Avicel PH 102 and Aerosil 200 in poly ethylene glycol can be given according to values of Phi (Φ) as given by Spireas et.al. L f = (1/R) Based on this equation, Lf is calculated by using different R values. DISCUSSION Fig-2 demonstrates the FT-IR spectra of pure drug (Mefenamic acid) which shows characteristic peaks at , , , and cm -1 represents C-H bending (Aromatic), O-H bending, C-O stretching, C=C stretching (Aromatic), N-H bending along with C-N stretching respectively. Among which C-H bending (Aromatic), O-H bending, C-O stretching N-H bending along with C-N stretching are responsible peaks for 94 P a g e

16 the formation of acidic group (COOH) which was attached to an aromatic ring of Mefenamic acid. From the MOA of NSAID s (Anthranilates/Fenamates group) it was observed that the acidic group (-COOH) attached to an aromatic ring was responsible for the COX inhibiting activity of Mefenamic acid. Hence when fig-2 (pure drug-mefenamic acid) was compared with fig-3, 4 and 5 (drug with mixture of excipients) we can conclude that there is no characteristic change in the above peaks represents there is no any incompatibilities with the excipients utilized in the formulation of liquisolid compacts, leads FT-IR results were confirming there were no any chemical interactions between the pure drug and physical mixtures. Solubility of mefenamic acid in water, phosphate buffer 7.4, propylene glycol, PEG-400, Glycerin, SLS and Tween-80 was given in table-2. As shown in the table its solubility was found to be very poor in water (0.208mg/ml). In propylene glycol, the solubility of mefenamic acid was found to be 0.218mg/ml, which is slightly greater than that of water. This slight increase is probably through hydrogen bonding. It was found that the solubility of mefenamic acid was very high in PEG-400 (11.50mg/ml) compared with other nonvolatile solvents. This increase in solubility is due to the large non polar part and several hydroxyl groups in PEG were responsible for the enhanced solubility. Thus, among the solvents tested, PEG-400 could be a better choice as a non-volatile solvent. From the micromeritic properties it was observed that mefenamic acid drug alone due to its amorphous nature shows poor flow properties when compared to its physical mixture which shows good flow properties and passable. From the results of post-formulation parameters it was concluded that there should be certain amount of strength or hardness and resistance to friability for the tablet, so that tablet should not break during handling. However, it has also effect on drug dissolution. Average hardness of liquisolid tablet ranges from 5.7±0.19 to 7.3±0.34 kg/cm 2. Compactness of tablet may be due to hydrogen bonding between Avicel PH 102 molecules. As poly ethylene glycol is an alcoholic compound, it might show hydrogen bonding due to presence of hydroxyl groups and may contribute to compactness of compacts. Friability studies of liquisolid compacts are in the range of % to 0.210%. This indicates that acceptable resistance is shown by liquisolid compacts to withstand handling. In preparation of liquisolid compacts, liquid medications containing drug were adsorbed on the surface of carrier materials. When this system is exposed to the dissolution medium, drug located onto the surface of compacts dissolves fast and diffuses into dissolution medium. This can be assumed to be the cause of the burst effect observed. The concentration in liquid medication is an important aspect as it affects. As it was proved previously, increase in drug concentration in liquid medication, lower rate would observe. It was due to fact that at higher drug concentration, drug tends to precipitate within silica (Aerosil 200) pores. At higher amount of Aerosil 200 (Batch F12), was found to be retarded as compared to other batches. Increase in concentration of HPMC K100M might be responsible to get extended effect. This is reflected in batches F5, F6, and F11, F12. However, normal extended tablets showed faster as compared to liquisolid extended formulations. Liquisolid compacts containing Avicel PH 102 retards compared to compacts containing starch as carrier due to high wettability nature of Avicel. Although model independent methods are simple and easy to apply, they lack scientific justification. Hence different model dependent approaches (Zero order, First order, Higuchi, Korsemayer- Peppas plots) were performed for dissolution profile comparison of all liquisolid compacts. The results of these models indicate all liquisolid compacts follow Peppas model as best fit model. This is due to previously proved fact depending on R 2 value obtained from model fitting. From the results batches F6 and F12 showed more retarding effect. It is thus found that T 50 % value increases as concentration of HPMC K100M increases. Korsemayer - Peppas exponent (n) values of all liquisolid compacts are greater than 0.45 indicating non - Fickian diffusion. CONCLUSION From the results it was concluded that, percent was decreased with increase in the concentrations of HPMCK100M. The 12 hour profile may improve patient compliance with the usage of carrier and coating materials along with drug retarding polymer, such that the reduces in the gastric ph and increases when reaches to the intestinal ph which leads to decreased gastric cavity disorders and also the total amount was completely dissolved in to PEG which was further completely available to the intestinal medium after passage through GIT which was not observed in nonliquisolid extended tablets, because the drug in conventional dosage form was not in completely dissolved form hence causes gastric irritation. Based on the in-vitro studies, the data were fitted into different kinetic models shows zero order pattern followed by non-fickian transport mechanism. Drug profiles on model fitting follow Peppas model as best fit model which indicates drug diffusion in hydrated matrix and polymer relaxation. Among the models used for dissolution profile comparison, it was concluded that model independent methods were found to be very simple, but discrimination between dissolution profiles can be found using model dependent approach. 95 P a g e

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