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1220 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3 • Issue 4 • January-March 2011
International Journal of Pharmaceutical Sciences and Nanotechnology
Volume 3 • Issue 4 • January – March 2011
Research Paper
Preparation and Evaluation of Rapidly Disintegrating Glimepiride Tablets
Adel M. Aly1, Bassam I. Amro2 and Feras D. El Hajji233
1College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
2Faculty of Pharmacy, University of Jordan, Amman, Jordan. ABSTRACT: The objective of this work was to prepare Glimepiride (1 mg) rapidly disintegrating tablets (RDT) by
direct compression, and also, to evaluate Pharmaburst™ as a newly introduced diluent for this type of tablets, either alone
or in combination with other well known tablet excipients. Another goal was to study the stability, as well as, the in vivo
effects of selected formulations. Orange flavor was the most preferred flavor for the prepared rapidly disintegrating tablets
containing Pharmaburst™ as a single diluent. Pharmaburst™ alone is sufficient to produce rapidly (orally) disintegrating
tablets of Glimepiride with good physical characteristics, better compactability and shorter in-vivo and in-vitro disintegration
time. The prepared Glimepiride RDT were found to have faster onset of action than the conventional Glimepiride tablets.
Also, they were effective in lowering fasting blood glucose levels (FBG) in rabbits. Glimepiride RDT containing
Pharmaburst™ alone were found to be stable when subjected to accelerated stability conditions (40 °C / 75 % relative
humidity) for at least 3 months. Packaging the prepared Glimepiride RDT in 40 CC high density polyethylene (HDPE)
bottles with 2 grams silica gel desiccant canisters and rayon had provided sufficient protection for the tablets. The used
packaging system is believed to be very practical and convenient for elderly diabetic patients. It is also assumed to be
preferred by the manufacturers.
KEYWORDS: Glimepiride; Pharmaburst; Superdisintegrant; Rapidly disintegrating tablets
Introduction
Taste is the deciding factor regarding compliance to With the increase in the average human life, drug this dosage form. Usually, low-compression force is administration for elderly patients has become more applied to form a rapidly disintegrating tablets containing important. Due to a decline in swallowing ability with age, all or some of the following components: taste-masked a great many elderly patients complain that it is difficult to active ingredient; if the drug has an unpleasant taste, take medication in the form of tablets (Mallet, Sugihara diluents, sweetener, disintegrating agent, lubricant, glidant, and Ito et.al.). Recently, useful dosage forms, such as flavor and coloring agent (Rathbone, et.al., 2003). rapidly disintegrating or dissolving tablets have been Presence of water-soluble materials improves taste and developed and applied clinically (Sallam et.al1998., texture of the disintegrating tablets (Ishikawa, et.al., 1999, Ishikawa et.al., 1999, Shu et.al., 2002, Aly, 2003, and Sunada, et.al., 2002). Spray dried excipient base of Abdelbary, 2004, 2005, Aly et.al., 2005, and mannitol and a superdisintegrant can be prepared for compression with the drug for faster disintegration time Oshima,et.al.,). This dosage form can also improve (Mishra, et.al., 2006). compliance in children (Fukmi et.al., 2006), as well as, for local action within oral cavity as local anesthetics for Pharmaburst™ is a newly introduced polyols and toothache, cold sore, or teething product. Rapidly mainly co-processed sugar alcohols (carbohydrates), with disintegrating tablets (RDT) may also be another option in other materials (SPI Pharma newsletter, 2002; emergency (Chue et.al., 2004). Camphor sublimation method (Aly et.al., 2005 Koizumi 1997) has been proved Glimepiride is approved by the Food and Drug
to be effective for the production of tablets of higher Administration (FDA) for “once-daily use as monotherapy or in combination with insulin to lower blood glucose in diabetes mellitus by binding to β-cell ATP dependent * For correspondence: Adel M. Aly, potassium channel. It has a long duration of effect with a half-life of about 5 hours, allowing once daily dosing and therapy improving compliance (Katzung, 2001). Adel M. Aly et.al. : Preparation and Evaluation of Rapidly Disintegrating Glimepiride Tablets 1221
The main objective of this work was to prepare orange, cherry, strawberry, golden syrup, and banana Glimepiride (1mg) rapidly disintegrating tablets by direct flavors were tested for tablets including Pharmaburst as the compression, and to evaluate Pharmaburst™ as a newly single diluents. Glimepiride (1%) was mixed manually for introduced diluent for this type of tablets, either alone or in two minutes with Pharmaburst and then sifted through combination with other well known diluent. Also, to study 850μm mesh sieve. Aspartame (4%), magnesium stearate the physical properties of the prepared tablet formulations (2%) and flavor (2%) (seven formulas each contains one to select the most suitable formula for stability, as well as, of the mentioned above flavours) were mixed for 10 minutes in a double cone blender (Erweka® AR400, Germany), sifted through 850 μm mesh sieve and Experimental
compressed into 100mg tablets on a rotary tablet press (Cadmach® 16 stations, India) fitted with an octagon Materials
Glimepiride (USV Limited, India), Pharmaburst™ (polyols Glimepiride is an odorless drug, and was found and mainly co-processed sugar alcohols,carbohydrates) tasteless at the used concentration (1 mg/tablet). Twenty C-1 (SPI Pharma), Mannitol (Mannogem™), Lactose five subjects (11 females and 14 males, 20 to 61 years old) monohydrate fast-flow, Lactose DCL 21, Sorbitol DC, examined the taste of each formula. For safety issues Magnesium stearate, Aspartame, Crospovidone Glimepiride was substituted with 1 mg of the diluents in (Polyplasdone-XL® and Polyplasdone-XL 10®), Sodium each formula. Evaluation scale was by describing the taste starch glycolate (Primogel®), Croscarmellose sodium as excellent, good, acceptable, and bad (Table1). (AcDiSol®), Polacrilin potassium (Amberlite), lemon flavor, tutti-frutti flavor, orange flavor, golden syrup Another five tablet formulations containing the same flavor, banana flavor, cherry flavor and strawberry flavor, ingredients but using different water-soluble diluents, 91%, and also, the packaging materials consisting of 40 CC namely; Sorbitol DC (A2), lactose monohydrate fast-flow high-density polyethylene (HDPE) bottles, 33 mm child (A3), lactose DCL 21 (A4), and mannitol (A5) in resistant caps (CRC), rayon and 1 g silica gel canisters, as comparison with the previously prepared formula that well as, Glorion® 1mg tablets, were kindly obtained from includes Pharmaburst™ C-1 (A1). Orange flavor (2%) was Hikma Pharmaceuticals, Amman, Jordan. All other added as it was the best according to the results of the taste materials used in this study were of analytical grade. Moreover, another Glimepiride 1mg tablet formulae including Pharmaburst (76%) with different well known disintegrants (15%) namely; AcDiSol (B1), Primojel (B2), Preparation of Glimepiride Tablets with
Polyplasdone XL (B3), Polyplasdone XL-10 (B4), or Pharmaburst
Amberlite (B5), were prepared applying the same previous Aiming for the production of Glimepiride (1mg) tablets procedures, in order to study the effect of their inclusion on with acceptable taste and oral rapidly disintegrating properties seven flavors, namely; lemon, tutti-frutti, Table 1 The results of taste evaluation for Glimperide (1mg) tablets containing Pharmaburst™
Taste result
Excellent Good Acceptable
Golden syrup
Tutti-frutti
Strawberry
1222 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3 • Issue 4 • January-March 2011

Evaluation of the Prepared Tablets
solvent for 10 minutes then sonicated for 15 minutes then passing through 0.45 μm PTFE membrane filter. Each of Uniformity of Weight
the standard and sample solutions were injected to the Twenty tablets taken randomly were weighed individually HPLC system, using column (Venusil XBP) C18 100 °A and the average weight, the standard deviation, and the (250 X 4.6 mm), 5 μm. The flow rate was 1.0 ml/min; with coefficient of variation percent, C.V. %, were calculated a wavelength of 228 nm; and injection volume of 20 μm. according to the USP. The thickness of the prepared tablets The Mobile phase was prepared by mixing phosphate was measured using thickness caliper (Mitutoyo® CD- buffer solution (monobasic sodium phosphate (NaH 15B, England) for 10 randomly selected tablets. and ortho-phosphoric acid) with equal volume of Hardness and Friability
acetonitrile, and then pH was adjusted to 2.2 ± 0.05 with phosphoric acid. The crushing strength (hardness) for randomly selected 10
tablets was measured by the hardness tester (Dr. System suitability: The relative standard deviation (RSD)
Schleunger Pharmatron®, Switzerland). The plunger speed
for five replicate injections of Glimepiride standard was 20 mm/minute. It was aimed to fix the hardness of all solution was not more than 2.0 %. Tailing factor for The friability test was performed for 20 tablets at 25 The % concentration of glimipride was calculated rpm for 4 minutes (European Pharmacopoeia, 2006) using a friabilator (Erweka® TA100, Germany), Disintegration Time
Disintegration Time in the Oral Cavity
The time required for complete disintegration of a tablet in the oral cavity, over the tongue (without allowing the For content uniformity test the difference was only in tongue to move), was collected from six healthy volunteers administered each formula at 24 hours intervals. The end point is the exact time required for complete disintegration Assay linearity: Different concentrations of the standard
of the tested tablet (Abdelbary, et.al., 2005). For safety were prepared and tested for HPLC peak area. Considering issues Glimepiride was substituted with 1 mg of the diluent 0.2 mg/ml concentration of the standard sample of Glimepiride to be 100 %, other concentrations represent 25 Disintegration Time in the Disintegration time apparatus
%, 50 %, 75 %, and 200 % of standard. Each concentration point was correlated with its specific peak area, and linear The test was performed by the disintegration time correlation equals 1 was resulted, which prove the assay apparatus (Erweka® ZT502, Germany) at 37 °C, 800 ml Wetting Time and Water Absorption Ratio
Stability Study
A piece of tissue paper (Whatman® number 1 filter paper The stability study of the prepared Glimepiride tablets was 10.75 X 12.00 mm) folded twice was placed in small performed by exposing to accelerated stability conditions culture dish containing 6 ml of water. A tablet was placed and detecting the physical and chemical changes on tablets. on the paper and the time for complete wetting was In addition, the suitability of the packaging system can be measured. The tablet was weighed before and after evaluated by filling 100 tablets per 40 CC HDPE bottle, wetting. Water absorption ratio was calculated using and 2 g silica gel canisters were added to each bottle as desiccant. The neck space of the bottle was occupied by rayon to minimize mechanical stress on tablets during R = 100(Wa-Wb) / Wb ….(1) handling. Each bottle was then thermally sealed and (Wb) and (Wa) are the weight before and after capped by a 33 mm CRC cap. The bottles were charged water absorption, respectively. The test was performed into a stability chamber (Votsch®, Germany) at 40 ± 2 °C separately on 6 tablets of each formula. and 75 ± 5 % relative humidity. Samples were withdrawn after 1 and 3 months exposure. Tablets were evaluated Drug Content Uniformity Tests
physically by all the previously mentioned tests. Standard solution (0.2 mg/ml) was prepared by accurately weighing 20 mg of Glimepiride dissolved in 100 ml In-vivo Study
solvent (Acetonitrile in water in 80: 20 ratio) by sonication Experimental animals: French rabbits weighing between
for 15 minutes. Each sample solution (0.2 mg/ml) was 1.0 and 2.0 Kg were involved in the study. The rabbits prepared by shacking 10 tablets individually with 50 ml were maintained on commercial diet (with free water). Adel M. Aly et.al. : Preparation and Evaluation of Rapidly Disintegrating Glimepiride Tablets 1223
They were acclimated to the laboratory conditions before banana. Therefore, orange flavor will be used for the The aim of the in-vivo study is to compare the glucose Physical Properties Results of Glimepiride 1mg
lowering (hypoglycemic) effect of the following three Tablets Containing Water Soluble Diluents
1. Glimepiride 1mg rapidly disintegrating tablet…. The average thickness of the compressed tablets of formulae from A1 to A5 lies within the range of 1.97 to 2.29 mm (Table 2). The thickness of the prepared tablets were found to be thin and flat which are preferred for (Glorion®1mg– Hikma Pharmaceuticals)… rapidly disintegrating tablet, to enable fast wetting by (Reference). saliva and short disintegration time. Friability results 3. Placebo orally disintegrating tablet (Substituting the showed that only tablets with Pharmaburst (A1) and tablets 1 mg Glimepiride in the test tablet with 1 mg with Mannitol (A5) were acceptable while tablets of Study design: Twelve rabbits were involved in the
Two approaches were followed to measure the experiment for each period. Three–way cross-over study, disintegration time; the in-vivo (oral) disintegration time is consisting of 3 dosing periods, with 7 days washing out the actual time during which the tablet disintegrates in the period between each were applied. They were randomly oral cavity, and the conventional disintegration time classified in into 3 groups, and each group includes 4 apparatus. The disintegration time results obtained for the rabbits. Each group will administer different tablet every five formulae (Figure 1) clearly indicate that formula A1 dosing period. Rabbits were fasted (with free water) for 12 (with Pharmaburst) revealed the shortest disintegration hours before dosing. Half an hour before dosing, initial (0 time. Oral disintegration time is within the recommended time) FBG was measured as an average of two readings. time for this type of tablets (< 60 second). Tablets of A3 Dosing had always started at 8:00 AM. Tablet formula (with lactose fast-flow) also have disintegration administration was carried out either by ingesting the time less than 60 seconds, but the time is longer than A1. whole reference tablet followed by 10 ml water, or by Disintegration time results for the rest formulae (A2, A4, keeping the whole test or control tablet in the oral cavity of and A5) exceeded the 60 seconds limit for the two the rabbit, keeping the mouth closed with continuous methods. Tablets of A4 (lactose DCL21) showed the checking till the tablet had completely disappeared longest disintegration time. This means that tablets with (disintegrated / dissolved). Sampling time intervals were: Pharmaburst™ are superior in disintegration time 1:00, 1:30, 2:00, 2:20, 2:40, 3:00, 3:30, 4:00, 5:00, and compared to the other tablet formulations. The relation 6:00 hour after administration. Blood samples were taken between the oral disintegration time and the wetting time from marginal ear vein of the rabbit, and blood glucose for tablets of group (A) is expressed in Figure 2. The level (BGL) was determined by glucose dehydrogenase wetting time for all tablets is always longer than oral cavity instrumental biochemical reaction (Accu-Check® Active, disintegration time. Tablets of A1 have the shortest wetting time, which means that Pharmaburst presents better hydrophilic and porous properties. Wetting time for Results and Discussion
Sorbitol tablets (A2) is extremely high, and also very high for lactose DCL21 tablets (A4). Taste Evaluation for Glimperide (1mg) Tablets
An inverse relationship could be observed between the Containing Pharmaburst™
oral disintegration time and water absorption ratio (Figure Glimepiride is an odorless drug, and was found tasteless in 2). It could be also, observed that tablets containing the used amount (1 mg/tablet) and may not have an effect Pharmaburst (A1) showed the highest water absorption the tablets taste. Thus, it was preferred to exclude ratio with the most rapid disintegration time. This means Glimepiride and perform the study on placebo tablets for that A1 tablets have comparatively the highest swelling the safety of the volunteers. The evaluation scale was from capacity and are the most porous tablets. excellent to bad, passing through good and acceptable. According to the results represented in table1, orange Glimepiride 1mg Tablets Containing
flavor was considered excellent by 64 % of the volunteers, Pharmaburst alone and with other Disintegrants
and it is the highest excellent result among other flavors, The thickness values, represented in Table 2, were in the so, orange flavor is the most preferred flavor by the range of 2.12 to 2.38 mm thickness and also considered volunteers. The other flavors included in this survey can be thin, i.e. promotes very rapid disintegration when in arranged according to taste preference as follows: orange > contact with water. Friability results show that tablets strawberry > cherry > golden syrup > lemon, tutti-frutti > containing Pharmaburst and AcDiSol (B1), as well as, 1224 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3 • Issue 4 • January-March 2011
those of Pharmaburst and Amberlite (B5) were friable, Disintegration time in the oral cavity for all tablets while the others B2, B3, and B4 tablets are acceptable. containing Pharmaburst is below 60 seconds. No significant improvement had occurred to oral Disintegration Time Results
disintegration time after inclusion of disintegrants. Disintegration time of B3 and B5 is slightly faster than A1, The used disintegrants, AcDiSol, primojel, polyplasdone however, it was longer with B4, and the longest with B1 XL and polyplasdone XL10 are considered and B2 by about 20 seconds than A1. superdisintegrants. Amberlite (polacrilin potassium) is considered a resin with good disintegration behavior According to the oral disintegration time results, tablets (Sunada, et.al., 2002). The relation between disintegration can be arranged from the shortest to the longest time as: B5 time results by each method of measurement for A1 and < B3 < A1 < B4 < B1 < B2. Wetting time is longer than B1 to B5 formulae is presented in Figure 3. oral cavity disintegration time for all tablet formulations. The relation between the oral disintegration time and the wetting time is expressed in Figure 4. Table 2 Physical properties of Gliperide (1mg) tablets prepared with single diluents.
Pharmaburst
Sorbitol DC
Lactose fast-
Lactose- DCL21
Mannitol
Parameter
flow (A3)
Weight (mg ± SD)
Thickness (mm ± SD)
Hardness (N ± SD)
Friability (%)
Disintegration time in oral
cavity (second ± SD)
In-vitro disintegration
time(second ± SD)
Wetting time
Water absorption ratio
Fig. 1 Disintegration time results for tablets containing Pharmaburst (A1), Sorbitol (A2),
Lactose fast-flow (A3), Lactose DCL21 (A4), or Mannitol (A5). Adel M. Aly et.al. : Preparation and Evaluation of Rapidly Disintegrating Glimepiride Tablets 1225
Fig. 2 Oral disintegration time versus wetting time for formulae containing Pharmaburst (A1), Sorbitol (A2),
Lactose fast-flow (A3), Lactose DCL21 (A4), or Mannitol (A5). Fig. 3 Oral disintegration time versus water absorption ratio for tablets containing Pharmaburst, (A1),
Sorbitol (A2), Lactose fast-flow (A3), Lactose DCL21 (A4), or Mannitol (A5). Fig. 4 Disintegration time results of tablets containing Pharmaburst alone (A1), with AcDiSol (B1),
Primojel (B2), Polyplasdone XL(B3), Polyplasdone XL10 (B4), or with Amberlite (B5). 1226 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3 • Issue 4 • January-March 2011
Tablets containing highly swellable disintegrants Packaging Glimepiride 1mg RDT in bottles is very (AcDiSol and primojel in B1 and B2 respectively) have the practical and convenient. Filling tablets into bottles is the highest water absorption ratio. These results can give an most preferred packaging process, because it is time saving explanation about disintegration action of Pharmaburst. It and less expensive than others. Since the mechanical may suggest that Pharmaburst has a good disintegrating strength for the tablets studied for stability (A1) is very capacity by mainly two mechanisms: swelling and wicking satisfactory, so filling the tablets in bottles would be easily applicable. For further mechanical protection on handling or transportation, rayon coil was added to fill the space From physical evaluation results for tablets with over the tablets. Pharmaburst and a disintegrating agent compared to tablets with Pharmaburst only, it seems that addition of Protection from moisture is generally very critical for disintegrants to aid lowering oral disintegration of drugs, especially for RDT. If high percent of moisture was Glimperide tablets containing Pharmaburst is of no absorbed by the RDT, this will lead to physical spoilage as significant advantage. Thus, formulating Glimepiride tablet softening or disintegration, and chemical spoilage rapidly disintegrating tablets with Pharmaburst alone with for the drug as enhanced degradation and decrease in no additional disintegrants are preferred, since powder assay. As a precaution, silica gel desiccants were added in compactability is almost the best, cost would be lower, and the bottles to protect the tablets from moisture during shelf-life, and even after opening the bottle. More moisture protection is attained by sealing the bottle thermally. Chemical Evaluation
Taking into consideration that Glimepiride is an Chemical evaluation was performed on Glimepiride 1 mg antidiabetic medicine, it is surely harmful for children. The rapidly disintegrating tablets (with Pharmaburst, A1), and child resistant cap used with this packaging system is Glimepiride 1 mg oral conventional immediate release assumed to provide avoidance of misuse of the drug by Content Uniformity Test
Physical Evaluation
Assay results for content uniformity of rapidly Physical results are summarized in Table 3. Upon studying disintegrating tablets was 100.2% (with RSD of 2.2). but the weight and thickness values for stability samples, it for conventional tablets was 99.8% (with RSD of 1.7). The could be observed that results are very close and there is two formulations were acceptable (within the 90 – 110 %). almost no change. Since the tablets did not gain weight upon exposure to the accelerated stability conditions, this Stability Study
means that the tablets did not absorb humidity. This is aided also by the unchanged thickness values. Hardness The stability of Glimepiride rapidly disintegrating tablets and friability results also are considered more or less the (containing Pharmaburst as single diluent – A1) was same as initial results. Thus, it could be concluded that the studied in high density polyethylene (HDPE) bottles final physical strength of Glimepiride RDT were kept upon package. Physico-chemical evaluation of the samples was exposure to the accelerated stability conditions up to 3 performed. Chemical evaluation can assess the stability of Glimepiride active material in this dosage form that containing Pharmaburst. Table 3 Physical properties of Gliperide (1mg) tablets containing Pharmaburst™ with disintegrants.
Primojel
Polyplasdone
Polyplasdone
Amberlite
Parameter
XL10 (B4)
Weight (mg ± SD)
Thickness (mm ± SD)
Hardness (N ± SD)
Friability (%)
Disintegration time in Oral cavity
In-vitro disintegration time
Wetting time (second ± SD)
Water absorption ratio (% ± SD)
Adel M. Aly et.al. : Preparation and Evaluation of Rapidly Disintegrating Glimepiride Tablets 1227
Figure 5 represents the relationship between the in- were 103.1 % and 98.7 %, respectively. There is no vitro disintegration, and the wetting time for the tablets decrease in assay values for the glimepiride in the rapidly initially and after stability study. For initial, 1 month and 3 disintegrating tablets compared to initial reading (97.9 %). months stability tablets, results are very close and no These results indicate that glimepiride is stable during significant changes could be detected. Results of in-vitro three months of exposure to accelerated conditions. conventional disintegration and wetting time are directly related to disintegration time in the oral cavity. In-vivo Study
Since no change had occurred to results of the tested Glimepiride 1mg was tested for in-vivo release from the parameters, oral disintegration time is not supposed to prepared rapidly disintegrating tablet, conventional change. Hence, about 23 seconds is the expected disintegration time for Glimepiride 1 mg rapidly (Glorion® 1mg) tablet and control (placebo tablets). The disintegrating tablet exposed to 40 °C / 75 % relative blood glucose concentration in rabbits was measured as an humidity in its final package. The above prediction for indication of the efficacy of Glimepiride tablets. Results of oral disintegration time is also aided by the unchanged blood glucose values are presented in tables 4 and Figure water absorption ratio for tablets after stability. 6. Analysis of variance (ANOVA) calculated (p-values) comparing the prepared Glimepiride RDT with the Chemical Evaluation
reference commercial (Glorion® 1mg) for each time Chemical evaluation includes assay test and dissolution. Assay results for the one and three months stability tablets Fig. 5 The relation between oral disintegration time and wetting time of tablets containing Pharmaburst alone
(A1) or with AcDiSol (B1), Primojel (B2), Polyplasdone XL(B3), Polyplasdone XL10 (B4), or with Amberlite (B5). Table 4 Physical properties of tablets containing Pharmaburst alone (A1)
Initial (A1)
Parameter
Weight (mg ± SD)
Thickness (mm ± SD)
Hardness (N ± SD)
Friability (%)
In-vitro disintegration time
Wetting time (second ± SD)
Water absorption ratio (% ± SD)
1228 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3 • Issue 4 • January-March 2011
Time (hour)
Fig. 6 Rabbits blood glucose concentration in mg/dl for test, reference, and control, vs. time.
Table 5 Blood glucose concentration (mg/dl) for the tested Glimepiride 1 mg tablet formulation
Glimepiride with
Glimepiride
Control (placebo)
Pharmaburst™ tablets (1)
(Glorion® 1mg) tablet (2)
Tablets (3)
p-values between
(1) and (2)
Time (hr).
0:00 102.25a
1:00 78.92b
1:30 64.00c
2:00 48.75d
2:20 45.83d
2:40 42.42c
3:00 40.42c
3:30 42.17a
4:00 39.83b
5:00 36.92c
6:00 36.08c
Considerable reduction in blood glucose levels for both the that the prepared Glimepiride rapidly disintegrating prepared and reference formula after 1 hour with p-values tablets is considerably more efficient in lowering blood of 0.07 reduced to 0.03 after 0.5hour and nearly less than glucose than reference (conventional tablets) especially 0.05 at all the tested time intervals. This indicates that during the first two hours. The faster disintegration of the significant difference between the prepared and the Glimepiride RDT may be the actual reason for faster onset commercial conventional tablets. Thus, it could be concluded of action and more effective in lowering fasting blood glucose levels (FBG) in rabbits. Adel M. Aly et.al. : Preparation and Evaluation of Rapidly Disintegrating Glimepiride Tablets 1229

Conclusion
Ishikawa T., Watanabey Y., Utoguchi N.and Matsumoto M. Preparation and evaluation of tablets rapidly disintegrating in Glimepiride RDT containing Pharmaburst™ alone were saliva containing bitter-taste-masked granules by the found to have faster onset of action than the conventional compression method. Chem Pharm Bull, 47(10): 1451-
Glimepiride tablets. Also, they were effective in lowering fasting blood glucose levels (FBG) in rabbits. The prepared Glimepiride RDT were found to be stable when subjected Ito A. and Sugihara M. Development of oral dosage form for to accelerated stability conditions (40 °C / 75 % relative elderly patients: use of agar as base of rapidly disintegrating humidity) for at least 3 months. Packaging the prepared oral tablets. Chem Pharm Bull, 44(11):2132-2136(1996).
Glimepiride RDT in 40 CC HDPE bottles with 2 g silica Katzung BG., Basic & Clinical Pharmacology. Eighth edition gel desiccant canisters and rayon had provided sufficient (International edition). New York: Lange Medical Books / protection for the prepared Glimepiride RDT tablets. McGraw-Hill Companies, Inc., Medical Publishing Division. (2001). Acknowledgments
Koizumi KI., Watanabe Y., Morita K., Utoguchi N., and The authors wish to thank Hikma Pharmaceuticals, Matsumoto M.New method of preparing high- porosity Amman, Jordan for the supplying of most of the utilized rapidly saliva soluble compressed tablets using mannitol with camphor, a subliming material. International Journal of
Pharmaceutics, 152: 127-131(1997).
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