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. Amro2andFeras 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
compressed into 100mg tablets on a rotary tablet press (Cadmach® 16 stations, India) fitted with an octagon
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 ofGlimepiride Tablets with
Polyplasdone XL (B3), Polyplasdone XL-10 (B4), or
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
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
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.
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
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 timeinOral 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.
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
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
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).
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). References
Mallet L. Caring for the elderly patient. J Am Pharm Assoc,
36(11): 628 (1996).
Abdelbary, G., Eouani, C., Prinderre, P., Joachiom, J., Reynier, J.
Mishra DN, Bindal M., Singh SK., and Vijaya Kumar SG., Spray
P., and Piccerelle, P., Determination of the in vitro
Dried Excipient Base: A Novel Technique for the
disintegration profile of rapidly disintegrating tablets and
Formulation of Orally Disintegrating Tablets. Chemical and
correlation with oral disintegration. International Journal of Pharmaceutical Bulletin.54 (1):99–102 (2006). Pharmaceutics. 292, 29-41(2005).
Oshima T., Sonoda R., Ohkuma M., Sunada H. Preparation of
Abdelbary, G., Prinderre, P., Eouani, C., Joachiom, J., Reynier, J.
rapidly disintegrating tablets containing itraconazole solid
P., and Piccerelle, P., The preparation of orally disintegrating
dispersions. Chemical & pharmaceutical bulletin, 55
tablets using a hydrophilic waxy binder. International Journal of Pharmaceutics. 278, 423-433(2004).
Rathbone M., Hadgraft J., and Robert M., Modified-release Drug
Aly AM, Semreen M., and. Qato MK. Superdisintegrants for
Delivery Technology. Marcel Dekker Inc., New York and
Solid Dispersion to produce Rapidly Disintegrating
Tenoxicam Tablets via Camphor Sublimation; Pharmaceutical Technology,29(1):68-75,(2005).
Sallam E., Ibrahim H.,. Dahab RA, Shubair M., and Khalil E.
Evaluation of fast disintegrants in terfenadine tablets
Aly AM., Preparation of Rapidly Disintegrating Ketorolac
containing a gas-evolving disintegrant. Drug Dev Ind Pharm,
Tromethamine Tablets by Direct compression and
24(6):501- 507 (1998).
Lyophilizaion, Arab Journal of Pharmaceutical Sciences, 2 (4):47-60 (2003).
Shu T., Suzuki H., Hironaka K., and Ito K. Studies of rapidly
disintegrating tablets in the oral cavity using co-ground
Chue P., Welch R., and Binder C., Acceptability and
mixtures of mannitol with crospovidone. Chemical &
disintegration rates of orally disintegrating Risperidone
pharmaceutical bulletin, 50 (2):193-198 (2002).
tablets in patients with Schizophrenia or Schizoeffective disorder. Canadian Journal of Psychiatry. 49 (10): 701-
Sugihara M. New oral dosage form for elderly patient. Chem Pharm Bull, 43(12): 1853-1861(1995).
Fukami J., Yonemochi E., Yoshihashi Y., and Terada K.,
Sunada H., and Bi Y., Preparation, evaluation and optimization
Evaluation of rapidly disintegrating tablets containing glycine
of rapidly disintegrating tablets. Powder Technology. 122:
and carboxymethylcellulose, International Journal of Pharmaceutics, 310 (1):101-109(2006).
Photodecomposition of Fluoxetine St. John’s University/College of St. Benedict Abstract Fluoxetine, also known as Prozac, is a widely marketed selective serotonin reuptake inhibitor, used to fight depression and anxiety. Recently, it has been observed that high levels of this pharmaceutical have been found in water sources prone to contamination. This is a concern for environmental
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