Comparative Study of Different Brands of Alprazolam

Table of contents

1. Introduction

lprazolam is a triazolobenzodiazepine. It is used in anxiety states and panic disorders [1,2]. Benzodiazepines are commonly used for deliberate self poisoning. It has been observed that in approximately one third of cases of deliberate self poisoning benzodizapenes are being used [3]. Alprazolam is a newer benzodiazepine and is used more commonly in overdose and no previous series of alprazolam poisonings were found. 14 case reports have been published including 5 reported deaths,2 in which alprazolam was ingested alone [4]. According to reports published by American Association of Poison Control Centers National Data Collection System indicated that alprazolam was involved in thirty four fatal deliberate self poisonings over ten years 1992-2001 compared with thirty fatal deliberate self poisonings involving diazepam [5]. This reveals significant alprazolam toxicity if prescribing practices in the United States (US) mirror Australian trends where diazepam is prescribed at five to ten times the rate of alprazolam. A British study showed the fatal toxicity index (deaths per million prescriptions) for diazepam was 4.0 compared with 5.9 for alprazolam. [6]. These data suggest that alprazolam is more toxic in overdose than other benzodiazepines.

In human liver this drug is metabolized by CYP3A enzymes to hydroxylated metabolites . 4-hydroxy alprazolam (4-OHALP) is the major and less active metabolite while ?-Hydroxy alprazolam (?-OHALP) is the Author ? ?: Faculty of Pharmacy Jinnah University for women Karachi. e-mails: [email protected], [email protected] minor and active metabolite. There is an intrinsic difference in the biotransformation of alprazolam in liver and brain. As P450 enzymes present in brain is one-10th to one-15th of liver [7] II. The official range of hardness stated in BP/USP is not less than 4.00 Kg of pressure is required to break a tablet, so all of the samples were tested for hardness.

2. d) Friability

To evaluate how well the tablets stands up to coating, packing, shipping and other processing friability test were conducted. From each brand of legal and illegal products, 20 tablets were taken and de dusted before weighing, after weighing the tablet were placed in drum of friability tester of which each tablet rotated 100 times. Finally 20 tablets of each brand were de dusted and reweighed and their percentage losses of weight were calculated. According to BP & USP the total weight loss should not be more than one percent and no tablet should show any type of break or crack.

Thickness Test: Thickness of above mentioned tablets including average , standard deviation, upper and lower limits are in accordance with BP/USP III.

3. Results

Weight Variation Test: Wt. variation test of alprazolam tablets proved statistically that all the tablets were in accordance to the BP/USP requirements. (Table -

4. Discusion

Uniformity of weight is compendia standard while hardness and friability are non compendia standards to assess the quality of the tablet. Friability is now included in USP.

5. a) Weight Variation

The table 1-3 indicate that weight variation values of Neuxam , Alp , Nervin showed that among three brands Alp has the highest value of the mean as compared to other brands. The requirements are met with weight variation qaccording to USP that is ,weight of not more than two tablets out of all brands differs from the average weight by more than 7.5% b) Friability

The table 3 and figure 5(%weight loss for Nexaum , Alp , Nervin ) showed that the Nexaum has the highest % weight lost and Alp has the lowest % weight lost when compared to Nervan.

All the three brands have less than 1% of weight lost which showed that these brands met the USP requirement.

6. c) Hardness

The official range of hardness stated in BP/USP is not less than 4.00 Kg of pressure is required to break a tablet, so all of the samples were tested for hardness.

The table and figure showed that Nervin has the highest hardness value and Alp has showed lowest hardness value. It shows that Alp showed to meet the USP requirement while the other two brands are beyond the USP limit.

Figure 1.
Material and Methods Alprazolam (0.5mg) tablets from the following thre different brands Neuxam (stand pharmaceuticals)Batch P0315E Alp (Hilton pharamceuticals) Batch 108891 Nervin (Werrick Pharmaceuticals) Batch 1971 Apparatus band equipments: 1. Analytical Balance 2. Rolex tablet hardness 3. Friability testerThe study used BP and other pharmacopeias to check the in vitro quality of alprazolam brands tablet using different analytical techniques and procedure described in the analytical techniques and procedures described in the pharmacopeias. For testing the physical parameters of alprazolam brands tablet Various instruments were used to measure content as well as qualities in general.a) General TestsQuality of alprazolam brands tablets were assessed in compliance with BP specifications. General tests include weight variation, tablets friability . b) Weight Variation Test Weight variation test of above mentioned tablets should be in accordance to the BP/USP requirements that not more than two tablets out of 20 tablets should cross ±7.5 % deviation.
Figure 2. A
Journals Inc. (US)
Figure 3. Table A :
A
Dosage form Average Percentage
weight deviation
Uncoated 80 mg or less 10
and film coated More than 80 mg but
tablets less than 250 mg 7.5
250 mg or more 5
c) Hardness
Figure 4. Table 1 :
1
Different Brands
Tablets Neuxam Alp Nervin
1 179 195 165
2 173 199 158
3 180 200 150
4 178 200 156
5 180 202 159
6 190 200 156
7 190 203 151
8 178 205 156
9 179 198 160
10 176 205 154
11 173 200 160
12 176 195 158
13 180 199 151
14 177 203 156
15 173 198 150
Figure 5. Table 2 :
2
Tablets Average Standard Upper limit Lower limit
(Gm) deviation (X+3S) (X-3S)
Neuxam 0.17985 0.005687 0.196911 0.162789
Alp 0.20025 0.002712 0.2083 0.19211
Nervin 0.15665 0.004308 0.16957 0.1437
Table 3 : Weight Variation Test
Tablets Result (Gm) BP/USP Specification Deviation from BP/USP Specification
Neuxam 0.17985
Alp Nervin 0.20025 0.15665 Deviation should be ±7.5% Within specified limit
Figure 6. Table 4 :
4
Tablets Neuxam Alp Nervin
1 3.3 3.2 3.2
2 3.4 3.1 3.2
3 3.3 3.2 3.2
4 3.2 3.1 3.2
5 3.5 3.1 3.1
6 3.3 3.1 3.1
7 3.3 3.1 3.1
8 3.5 3.1 3.1
9 3.4 3.1 3.1
10 3.3 3.1 3.1
Figure 7. Table 5 :
5
Average Standard Upper limit Lower limit (X-
Tablets Thickness mm deviation (X+3S) 3S)
Neuxam 3.35 0.09 3.64 3.05
Alp 3.12 0.04 3.246 2.99
Nervin 3.14 0.05 3.29 2.98
Figure 8. Table 6 :
6
Year 2014
27
Volume XIV Issue III Version I
( B )
Tablets Neuxam Alp Nervin Medical Research
1 2 3 4 5 6 7 7.69 5.05 6.14 7.40 7.88 7.306 7.16 2.19 2.5 2.47 2.41 2.21 2.05 1.92 12.2 12.0 11.7 15.2 12.1 10.2 13.2 Global Journal of
8 7.73 2.73 14.9
9 7.60 2.45 13.2
10 3.91 1.95 13.8
Note: © 2014 Global Journals Inc. (US)
Figure 9. Table 7 :
7
Tablets Average (Kg) Standard deviation Upper limit (X+3S) Lower limit (X-3S)
Neuxam 6.7866 1.335725 10.79377 2.779426
Alp 2.288 0.265949 3.085847 1.490153
Nervin 12.85 1.524795 17.42439 8.275615

Appendix A

  1. Experience with 732 acute overdose patients admitted to an intensive care unit over six years. A Henderson , M Wright , S M Pond . Med J Aust 1993. 158 p. .
  2. Differential metabolism of alprazolam by liver and brain cytochrome (P4503A) to pharmacy-ologically active metabolite. Pharmacogenomics. H V Pai , S C Upadhya , S J Chinta , S N Hedge , V Ravindranath . J 2002. 2 p. .
  3. A comparison of the safety and efficacy of alprazolam versus other agents in the treatment of anxiety, panic, and depression: a review of the literature. J M Jonas , M S Cohon . J Clin Psychiatry 1993. 54 p. . (Suppl)
  4. Alprazolam for panic disorder. M Abramowicz . Med Lett Drugs Ther 1991. 33 p. .
  5. Fatal poisonings attributed to benzodiazepines in Britain during the 1980s. M Serfaty , G Masterton . Br J Psychiatry 1993. 163 p. .
  6. 1992 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. T L Litovitz , K C Holm , C Clancy , B F Schmitz , L R Clark , G M Oderda . Am J Emerg Med 1993. 11 p. .
  7. Captopril overdose resulting in hypotension. W L Augenstein , K W Kulig , B H Rumack . JAMA 1988. 259 p. .
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Date: 2014-01-15