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1 UK Journal of Pharmaceutical and Biosciences Vol. 2(2), 08-15, 2014 RESEARCH ARTICLE UK Journal of Pharmaceutical and Biosciences Available at Formulation and Assessment of Mouth Dissolving Tablets of Repaglinide-β- Cyclodextrin Complex Lakahan Chadar 1*, Vaibhav Shukla 1,2, S K Jain 3 1 Oriental College of Pharmacy, Bhopal , (M.P.), India 2 Department of Pharmaceutical Sciences, Dr. K.N. Modi University, Newai, Tonk , (Rajasthan), India 3 Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar , (M.P.), India Article Information Received 24 January 2014 Received in revised form 01 April 2014 Accepted 02 April 2014 Keywords: Repaglinide Crosscarmellose sodium Crosspovidone Sodium Starch Glycolate Mouth dissolving tablets * Corresponding Author: kidspharma@gmail.com Tel.: Abstract The present study was carried out to develop mouth dissolving tablets of Repaglinide with a rationale of providing better patient compliance, will serve to provide effective mode of treatment to elderly, impaired and noncooperative patient suffering from diabetes. The Repaglinide-βcyclodextrin was prepared in order to increase the solubility of drug. The inclusion efficiency of different ratios of Repaglinide-β-cyclodextrin was calculated, that shows the inclusion efficiency of 1:1 molar ratio is highest. The mouth dissolving tablets of Repaglinide (RCT1 to RCT5) were prepared by direct compression method using super disintegrants, for optimization of the diluents. The value of pre-compression of blends and postcompression tablets exhibited satisfactorily results. The formulation RCT3 complied with all the physical parameters such as hardness, friability and disintegration time, and taken for further studies. Nine different formulations (RCT6 to RCT14) were prepared by using various concentration of super disintegrant namely Crosscarmellose sodium, Crosspovidone and Sodium Starch Glycolate. Among all formulations studied, formulation RCT9 having crospovidone as disintegrant showed 56.5% drug release in 5 min. Therefore crospovidone is considered best superdisintegrant among Sodium starch glycolate and Crosscarmellose sodium. 1 Introduction Tablet is the most popular among all dosage forms existing today because of its convenience of self administration, compactness and easy manufacturing; however hand tremors, dysphasia in case of geriatric patients, the underdeveloped muscular and nervous systems in young individuals and case of uncooperative patients, the problem of swallowing is common phenomenon which leads to poor patient compliance 1. To overcome these drawbacks, mouth dissolving tablets (MDT) or orally disintegrating tablets (ODT) has emerged as alternative oral dosage forms. These are novel types of tablets that disintegrate/dissolve/ disperse in saliva within few seconds. According to European Pharmacopoeia, the MDT should disperse/disintegrate in less than three minutes. The basic approach used in development of MDT is the use of superdisintegrants like Cross linked carboxymelhylcellulose (Croscarmeliose), Sodium starch glycolate (Primogel, Explotab). Polyvinylpyrrolidone (Polyplasdone) etc. which provide instantaneous disintegration of tablet after putting on tongue, thereby releasing the drug in saliva. The target populations for these new Mouth dissolving dosage forms have generally been pediatric, geriatric, and bedridden or developmentally disabled patients. Patients with persistent nausea, who are traveling, or who have little or no access to water are also good candidates for mouth dissolving tablets 2. In the near future, other patient populations will also be targeted. A novel application for mouth dissolving tablets is in veterinary medicine, for example, to avoid pilling a cat. With Mouth dissolving dosage forms increasingly available, it will be likely that prescribers will recommend such products for their noncompliant patients. The ease of administration of a Mouth dissolving tablet, along with its pleasant taste, may encourage a patient to adhere to a daily medication regimen. Although a Mouth Dissolving Tablets may not solve all compliance issues, it may be enough of an advance to be of therapeutic significance.
2 Mouth dissolving tablets offering advantages over liquid and traditional dosage forms as it provides the convenience of a tablet formulation, while also allowing the ease of swallowing provided by a liquid formulation. Mouth dissolving tablets allow the luxury of much more accurate dosing than the primary alternative, oral liquids. A major claim of the some mouth dissolving tablets is increased bioavailability compared to traditional tablets. Because of dispersion in saliva while still in the oral cavity, there can be pre-gastric absorption from some formulations in those cases where the drug dissolves quickly. Buccal, pharyngeal and gastric regions are all areas of absorption of the many formulations 3. However, other formulations show nearly identical plasma-concentration profiles. Any pre-gastric absorption avoids first pass metabolism and can be a great advantage in drugs that undergo a great deal of hepatic metabolism. However, if the amount of swallowed drug varies, there is the potential for inconsistent bioavailability. While the claimed increase in bioavailability is disputable, it is clear that the major advantage of these formulations is convenience 1. Pharmaceutical marketing is another reason for the increase in available Mouth dissolving products. As a drug entity nears the end of its patent life, it is common for pharmaceutical manufacturers to develop a given drug entity in a new and improved dosage form. A new dosage form allows a manufacturer to extend market exclusivity, while offering its patient population a more convenient dosage form or dosing regimen. In this regard, Mouth dissolving tablet formulations are similar to many sustained release formulations that are now commonly available. An extension of market exclusivity, which can be provided by a mouth dissolving dosage form, leads to increased revenue, while also targeting underserved and under treated patient populations. Although the cost to manufacture these specialized dosage forms exceeds that of traditional tablets, this additional cost is not being passed on to the consumer. Therefore, cost is generally not an issue when recommending these new dosage forms. The present invention relates to the development of mouth dissolving tablet of Repaglinide-β-cyclodextrin. Repaglinide is an oral hypoglycemic agent especially useful for the treatment of diabetes type II. It induces the rapid onset short lasting insulin release. It acts in an analogous manner by binding to sulfonylurea receptor as well as to other distinct receptors. Repaglinide close the ATP dependant K channel into membrane of β cells which depolarizes the β cells and results in opening of the cell s calcium channel, which in turn induces calcium influx dependent insulin secretion. Repaglinide has poor aqueous solubility, which is the rate-limiting step for absorption of drug. Many attempts or means have been used to increase water solubility of Repaglinide. Solubility can be increased by forming a with cyclodextrin. Cyclodextrin enhances the aqueous solubility of drugs through inclusion ation which will be used to formulate mouth dissolving tablets. This will not only enhance the bioavailability of the drug but also reduce the onset of action due to fast absorption of drug from GIT as drug will be available as ready to absorption i.e. in solution form from the mouth cavity itself. 2 Materials and Methods 2.1 Materials Repaglinide gifted from Macleods Pharmaceutical Limited Mumbai, India, was off white, odourless powder. 2.2 Methods Preparation and characterization of Repaglinide-β Cyclodextrin Preparation of physical mixtures and the solid inclusion For physical mixtures, Repaglinide and β-cyclodextrin were weighed accurately at 1:1, 2:1 and 3:1 molar ratios mixed thoroughly by trituration in a mortar and sieved through 0.25 mm sieve. All physical mixtures were stored in dessicator until further evaluation. The inclusion of Repaglinide with β- cyclodextrin was prepared at 1:1, 2:1 and 3:1 molar ratios by wetting the physical mixture in a mortar with a minimum volume of ethanol and water (1:1 v/v) mixture and kneading thoroughly with a pestle to obtain a paste, which was then dried under vacuum at room temperature, sieved through 0.25 mm sieve and stored in a dessicator until further evaluation Inclusion efficiency The kneaded and its physical mixtures (25 mg) were placed in 25-mL volumetric flasks. Methanol (10 ml) was added, mixed thoroughly and sonicated for 30 min. The volume was made up to the mark with methanol. The solution was suitably diluted with the same solvent and spectrophotometrically assayed for drug content at nm Dissolution studies Dissolution studies were performed in phosphate buffer (ph 6.8, 900 ml) at 37±0.2 C, using USP XXIII apparatus (Electrolab, India) with a paddle rotating at 50 rpm. Solid products, each containing 50 mg of drug, were subjected to dissolution. At fixed time intervals, samples were withdrawn, filtered (Whatmann filter paper no. 41) and spectrophotometrically assayed for drug content at nm Preparation of mouth dissolving tablets containing a of Repaglinide with β-cyclodextrin UK J Pharm & Biosci, 2014: 2(2); 9
3 Mouth dissolving tablets were prepared by direct compression method using super disintegrants. Microcrystalline cellulose and lactose used as diluents. The equivalent to 1.5 mg of drug was taken and then mixed with directly compressible diluent and superdisintegrants in a container. Magnesium stearate and talc were mixed and blended with the initial mixture followed by compression of the blend. Compression was performed using 10 mm round, flat and plain single punch machine (Table 3) Pre-compression evaluation of powder blend Bulk density Bulk density was determined by placing the powders blend in a measuring cylinder and the total volume is noted. The weight of powder bed was determined by using digital weighing balance. Bulk density was calculated using the following formula: Bulk Density = Weight of the powder / Volume of the powder Tapped density Tapped density was determined by taking the dried powders in a measuring cylinder and measures the volume of powders after 100 tapping s and take weight of the total powders. Tapped Density = Weight of the powder / Tapped Volume of the powder Angle of repose Angle of repose was determined by measuring the height and radius of the heap of the powder bed. A cylindrical two side open tube of 6 cm length is place on graph paper. Powders are placed in the tube and slowly removed the tube vertically. With the help of scale the height and radius of the heap were measure and note. θ= tan -1 h / r Where, h = height of heap of granular bed, r = radius of heap of granular bed Compressibility index The compressibility was calculated using the equation: Percent compressibility or carr s index = [(tap - bulk)/tap] 100 Where bulk is the bulk density (g/ml) and tap is the tap density (g/ml) Evaluation of mouth dissolving tablets Friability test Friability of tablets was determined using Roche friabilator (Electolab, Mumbai). This device subjects the tablets to the combined effect of abrasions and shock in a plastic chamber revolving at 25 rpm and dropping the tablets at a height of six inches in each revolution. Preweighed sample of tablets was placed in the friabilator and were subjected to 100 revolutions. Tablets were dedusted using a soft muslin cloth and reweighed. The friability is given by the formula: F = (1 - Wo/W) x 100 Where, Wo is the weight of the tablets before the test and W is the weight of the tablet after the test Hardness Hardness or tablet crushing strength (Fc) (the force required to break a tablet in a diametric compression was measured using Monsanto hardness tester Drug content Four tablets were powdered and the blend equivalent to 6 mg of Repaglinide was weighed and dissolved in suitable quantity of phosphate buffer of ph 6.8. The solution was filtered, suitably diluted and the drug content was analyzed spectrophotometrically at 243 nm. Each sample was analyzed in triplicate Measurement of liquid uptake A glass petridish was partially filled with water and a tablet was placed on the surface of a band of filter paper supported on a glass slide. The uptake of water occurred from the lower surface of the tablet. The time required for water to reach the center of the upper surface of the tablet was noted as wetting time Disintegration Time The disintegration time (DT) was measured using a modified disintegration method, which is reported by Gohel et al. (2007) for mouth dissolving tablets. For this purpose, a petri dish (10-cm diameter) was filled with 10 ml of water. The tablet was carefully put in the center of the petridish and the time for the tablet to disintegrate completely into fine particles was noted In-vitro dissolution study The in-vitro dissolution study was carried out in the USP dissolution test apparatus (Dissolution tester USP) type 2 (paddle). The dissolution medium (900 ml, ph 6.8 buffer solution) was taken in a covered vessel and the temperature was maintained at 37±0.5 C. The speed of the paddle was set at 75 rpm. Sampling was performed at every 5-min interval. For each sample, 5 ml of the dissolution medium was withdrawn and immediately this volume was replaced with the same amount of fresh dissolution medium (Buffer ph 6.8, 37±0.5 C). The sample was withdrawn and diluted with buffer UK J Pharm & Biosci, 2014: 2(2); 10
4 solution (ph 6.8) and analyzed in the UV spectrophotometer (UV Shimadzu Corporation) at 243 nm. All the results were performed in triplicate Formulation of mouth dissolving tablets to assess effect of disintegrants Nine different formulations (RCT6 to RCT14) were prepared by using various concentration of super disintegrant namely Crosscarmellose sodium, Crosspovidone and Sodium Starch Glycolate (Table 8). It was decided to adopt the most simple direct compression process for manufacturing. All the excipients were mixed uniformly with drug as per the qualities given in table 3 and compressed as discussed in previous section. Tablets blends were evaluated for bulk density, tapped bulk density, compressibility index and angle of repose. The compressed tablets were then evaluated for various physical tests like friability, hardness, weight variation, wetting time, drug content and in-vitro dissolution study by using standard procedures Results and Discussions 3.1 Preparation and characterization of Repaglinide-β Cyclodextrin The Repaglinide-β-cyclodextrin was prepared in order to increase the solubility of drug. The and physical mixture of Repaglinide and β- cyclodextrin were prepared in different ratios of drug and β- cyclodextrin (1:1, 2:1 and 3:1) and inclusion efficiency of different ratios was calculated, that shows the inclusion efficiency of 1:1 molar ratio is highest (Table 1). Dissolution study of drug, physical mixture and Repaglinide - β- cyclodextrin have shown in table 2 that showed is more soluble than drug and physical mixture. 3.2 Preparation of mouth dissolving tablets containing a of Repaglinide with β-cyclodextrin The pharmacokinetic data revealed that Repaglinide is low permeable drug and less water soluble. Hence the basic aim of the formulation was to release the drug from the formulation instantly in water soluble form. The values of pre-compression parameters evaluated, were within prescribed limits and indicated a good free flowing property (Table 4). The data obtained from post-compression parameters such as weight variation, hardness, friability, wetting time, drug content and in vitro disintegration for prepared tablets were satisfactorily (Table 5 & Table 6). The results of pre-compression and post-compression indicate that product complied with the physical parameters. The formulation RCT3 exhibited good flow properties, less disintegration time (43 sec) and optimum dissolution rate (Table 7) compared to other formulations. Table 1: Inclusion efficiency of the drug and its preparation Type 1:1 molar ratio Inclusion Efficiency (%) 2:1 molar ratio 3:1 molar ratio Physical mixture 97.2 ± ± ±0.3 Kneaded 99.5 ± ± ± 0.4 Table 2: Dissolution profile of drug, physical mixture and Time (min) Cumulative % Drug Release Drug Physical Mixture Complex ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±1.02 Table 3: Composition of mouth dissolving tablets with different ratio of directly compressible diluents Ingredients (mg) RCT1 RCT2 RCT3 RCT4 RCT5 Repaglinide-cyclodextrin Lactose SD Microcrystalline cellulose Starch Crosscarmellose sodium Magnesium sterate Aspartame Vanillin flavour Sodium lauryl sulphate In order to have improved product performance several experiments were performed varying few of the functional excipients. Batch RCT3 UK J Pharm & Biosci, 2014: 2(2); 11
5 complied with all the physical parameters such as hardness, friability and disintegration time. So ratio of lactose and microcrystalline cellulose 3:4 was optimized and taken for further studies. 3.3 Formulation of mouth dissolving tablets to assess effect of disintegrants To point out disintegrants influence on the properties of directly compressible tablets among the various controls carried out throughout the operating procedure. The following parameters such as flow ability of blend, %compressibility of blend, physical properties of tablets were considered to optimize the formulation: Table 4: Precompressional parameters of powder blend used in the Optimization of directly compressible diluents The present investigation was undertaken to fabricate and evaluate a fast disintegration tablets of Repaglinide by direct compression method. Super disintegrants at different concentration levels were used to assist disintegration. Nine different formulations (RCT6 to RCT14) were prepared by using various concentration of super disintegrant namely Crosscarmellose sodium, Crosspovidone and Sodium Starch Glycolate, employing direct compression method. Bulk densities of various formulations were varied between 0.46 to 0.52 (gm/cm 3 ). The angle of repose values also varied from 26 to 34 (Table 9). Among all the formulation RCT6 and RCT9 exhibited good flow properties. In all the formulations, the hardness test indicated good mechanical strength, whereas friability is less than 1%, which indicated that the Formulation Angle of repose (θ) Bulk density (gm/cm 3 ) % Compress Flow property tablets had a good mechanical resistance (Table 10). Drug content was found to be high ( 98.11%) and uniform in all the tablets. Table 7: Drug release profile of tablets RCT1 33± ± ±0.25 Fair RCT2 30± ± ±0.17 Poor RCT3 26± ± ±0.65 Good RCT4 29± ± ±0.38 Fair RCT5 32± ± ±0.58 Poor Table 5: Post compression parameters of directly compressible diluents tablets Formulation % Friability Hardness (kg/cm 2 ) % Weight variation RCT1 1.2± ± ±5.82 RCT2 0.9± ± ±5.65 RCT3 0.6± ± ±4.48 RCT4 0.8± ± ±4.53 RCT5 1.0± ± ±5.62 Table 6: Post compression parameters of directly compressible diluents tablets Formulation Disintegration time (sec.) %Drug content (mg/tab) Wetting time (sec) RCT1 48± ± ±0.75 RCT2 45± ± ±0.54 RCT3 43± ± ±0.34 RCT4 46± ± ±0.47 RCT5 49± ± ±0.64 Time (min) Cumulative % drug release RCT1 RCT2 RCT3 RCT4 RCT ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.25 The tablets were subjected for evaluation of the in vitro disintegration time (Figure 1 and 2). After evaluation it was observed that the time for all the formulations varied from 40 to 56 sec. It was observed that when crospovidone was used as disintegrants, the tablet disintegrated rapidly within a short time due to the easy swelling ability of crospovidone when compared with other tablets prepared using Crosscarmellose sodium and Sodium starch glycolate. It is observed that the disintegration time of the tablets decreased with an increase in the level of Crosscarmellose sodium and crospovidone. However, the disintegration time increased with an increase in the level of Sodium starch glycolate in the tablets. It indicates that the increase in the level of Sodium starch glycolate had a negative effect on the disintegration of the tablets. At higher levels, formation of a viscous gel layer by Sodium starch glycolate 10 might have formed a thick barrier to the further penetration of the disintegration medium and hindered the disintegration or leakage of the tablet contents. Thus, tablet disintegration is retarded to some extent with tablets containing Sodium starch glycolate when compared with the UK J Pharm & Biosci, 2014: 2(2); 12
6 disintegration time of the tablets containing crospovidone 11. These results suggest that using wicking type of disintegrants like crospovidone can decrease the disintegration time. The dissolution of Repaglinide from the tablets is shown in (Table 7 and Table 11). The dissolution process of a tablet depends on the wetting followed by disintegration of the tablet. Table 8: Composition of mouth dissolving tablets with different ratio of super disintegrant Ingredients (mg) RCT6 RCT7 RCT8 RCT9 RCT10 RCT11 RCT12 RCT13 RCT14 Repaglinide-cyclodextrin Lactose SD Starch Microcrystalline cellulose Crosscarmellose sodium Crosspovidone Sodium Starch Glycolate Magnesium sterate Aspartame Sodium Lauryl Sulphate Vanillin Table 9: Precompressional parameters of blends using different ratio of super disintegrant Formulation Angle of repose ( ) Bulk density (gm/cm 3 ) % Compressibility Flowability RCT6 27± ± ±0.34 Good RCT7 29± ± ±0.55 Fair RCT8 30± ± ±0.84 Poor RCT9 26± ± ±0.47 Good RCT10 29± ± ±0.87 Fair RCT11 30± ± ±0.31 Fair RCT12 31± ± ±0.55 Fair RCT13 34± ± ±0.24 Poor RCT14 33± ± ±0.66 Poor Table 10: Post-compressional parameters of tablets using different ratio of super disintegrant Formulation % Friability Hardness (kg/cm 2 ) Disintegration time(sec.) %Weight variation %Drug content Wetting time(sec) RCT6 0.7± ± ± ± ± ±0.19 RCT7 0.9± ± ± ± ± ±0.33 RCT8 1.1± ± ± ± ± ±0.68 RCT9 0.7± ± ± ± ± ±0.49 RCT10 0.9± ± ± ± ± ±0.6 RCT11 1.1± ± ± ± ± ±0.59 RCT12 0.6± ± ± ± ± ±0.81 RCT13 0.9± ± ± ± ± ±0.67 RCT14 1.0± ± ± ± ± ±0.49 UK J Pharm & Biosci, 2014: 2(2); 13
7 Table 11: Tablet release profile of tablets prepared with different ratio of super disintegrant Time (min.) Cumulative % drug release RCT6 RCT7 RCT8 RCT9 RCT10 RCT11 RCT12 RCT13 RCT ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.95 superdisintegrant among Sodium starch glycolate and Crosscarmellose sodium. Fig. 1: Photographs showing disintegration of optimized (RCT9) tablets in water at 30, 60 and 90 seconds Physical parameters confirmed to the requirements. Weight variation was found with in the specifications of I.P 96. The Average percentage deviation of 20 tablets from each formulation was remained within ±7.5%. Hardness of the all tablet formulations were observed in the range of 2.2 to 3.6 (kg/cm 3 ). Friability of selected formulations was found in the range of 0.6 to 1.0%. Drug content of all formulations were found in the range of % (Table 10). Selected formulations had disintegration time of less than one minute. Among the combination of superdisintegrants of Microcrystalline cellulose and Crospovidone showed the highest efficiency. 4 Conclusions Fig. 2: Photographs showing disintegration of drug tablets in water at 30, 60 and 90 seconds The rapid increase in dissolution of Repaglinide with the increase in Crosscarmellose sodium may be attributed to rapid swelling and disintegration 10 of the tablet into apparently primary particles 12. However, tablets prepared with Sodium starch glycolate disintegrate by rapid uptake of water followed by rapid and enormous swelling into primary particle, but more slowly due to the formation of a viscous gel layer by Sodium starch glycolate. Crospovidone exhibit high capillary activity and pronounced hydration, with little tendency to gel formation 10 and disintegrate the tablets rapidly but into larger masses of aggregated particles 12. Among all formulations studied, formulation RCT9 having crospovidone as disintegrant showed 56.5% drug release in 5 min. Therefore crospovidone is best The major problem of Repaglinide is poor bioavailability and its limited aqueous solubility, which may hinder dissolution. Results revealed that it is possible to enhance the dissolution rate and the bioavailability by preparing with β- cyclodextrin and direct compression technique using different superdisintegrants. The overall results indicate that formulation RCT9, which contains 5% Crospovidone, was better and that it satisfies all the criteria as a fast dissolving tablet. 5 References 1. Habib W, Khankari R, Hontz J. Fast-dissolving drug delivery systems, critical review in therapeutics. Drug Carrier Systems. 2000; 17(1): Chang R, Guo, X, Burnside BA, Couch R. Fast-dissolving tablets. Pharm Tech. 2000; 24(6): UK J Pharm & Biosci, 2014: 2(2); 14
8 3. Seager H. Drug-deliver products and the zydis fastdissolving dosage form. J Pharm Pharmacol. 1998; 50: Sharma PP, Sharma S, Khokra SL, Sahu RK, Jangde R, Singh J. Formulation, development and evaluation of sustained release matrix tablets containing salbutamol sulphate. Pharmacologyonline, 2011; 2: Sharma V, Sharma S, Khokra SL, Sahu RK, Jangde R, Singh J. Formulation, development and evaluation of Pregabalin sustained release matrix tablets. Der Pharmacia Lettre. 2011; 3(5): Atri S, Sharma S, Khokra SL, Sahu RK, Jangde R. Design and evaluation of HPMC and xathan gum-based sustained release matrix tablets of Theophyllie. Pharmacologyonline. 2011; 2: Patel HM, Suhagia BN, Shah SA, Rathod IS, Parmar VK. Preparation and characterization of etoricoxib-bcyclodextrin es prepared by the kneading method. Acta Pharm. 2007; 57: Gohel MC, Bansal G, Bhatt N. Formulation and evaluation of orodispersible taste masked tablets of Famotidine. Pharma Biol World. 2005; 3: Masih D, Gupta R. Formulation and Evaluation of Mouth Dissolving Tablets of Tolperisone. UK Journal of Pharmaceutical and Biosciences. 2013; 1(1): Bolhuis GK, Zuurman K, Wierik GH. Improvement of dissolution of poorly soluble drugs by solid deposition on a superdisintegrant: II, The choice of superdisintegrants and effect of granulation. Eur J Pharm Sci. 1997; 5: Rowe RC, Sheskey PJ, Weeler PJ. Editors. Handbook of pharmaceutical excipients. 4 th ed. London and Washington DC: The Pharmaceutical Press Zhao N, Augsburger LL. Functionality comparison of 3 classes of superdisintegrants in promoting aspirin tablet disintegration and dissolution. AAPS Pharm. Sci. Tech. 2005; 6: E UK J Pharm & Biosci, 2014: 2(2); 15
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