|Year : 2016 | Volume
| Issue : 3 | Page : 264-268
Formulation, characterization, and evaluation of orodispersible tablet of a model antidepressant drug
VG Jamakandi, Chetan Prakash Kalsannavar, SP Hiremath, FS Dasanakoppa, SS Kerur
Department of Pharmaceutics, KLEU's College of Pharmacy, Hubballi, Karnataka, India
|Date of Web Publication||21-Dec-2016|
Dr. V G Jamakandi
Department of Pharmaceutics, KLEU's College of Pharmacy, Vidyanagar, Hubballi, Karnataka
Source of Support: None, Conflict of Interest: None
Introduction: Paroxetine hydrochloride is used as the antidepressant drug of the selective serotonin reuptake inhibitor. It is used to treat depression resistant to other antidepressants, depression complicated by anxiety, panic disorder, obsessive-compulsive disorder (OCD). The objective of the present work is to formulate oral dispersible tablet dosage form using two different superdisintegrants.
Materials and Methods: Eight formulations (F1-F8) were prepared using two superdisintegrants in varied concentrations. The optimized formulations (based on %CDR) were further formulated by sublimating agent using camphor as sublimating agent (S1, S2).
Results and Discussion: All the formulated tablets were evaluated for physicochemical characteristics, drug content and in vitro drug release, dispersion time, and wetting time and the results were within the permissible limits.
Conclusion: Orodispersible tablets of paroxetine HCl were successfully formulated by employing direct compression and sublimation methods. From this investigation, it can be concluded that stable orodispersible tablets gave maximum %CDR with 10% camphor as sublimating agent and 8% crospovidone as super disintegrant.
Keywords: Camphor, crospovidone, direct compression, orodispersible tablets, paroxetine HCl, sodium starch glycolate, sublimation, superdisintegrants
|How to cite this article:|
Jamakandi V G, Kalsannavar CP, Hiremath S P, Dasanakoppa F S, Kerur S S. Formulation, characterization, and evaluation of orodispersible tablet of a model antidepressant drug. Indian J Health Sci Biomed Res 2016;9:264-8
|How to cite this URL:|
Jamakandi V G, Kalsannavar CP, Hiremath S P, Dasanakoppa F S, Kerur S S. Formulation, characterization, and evaluation of orodispersible tablet of a model antidepressant drug. Indian J Health Sci Biomed Res [serial online] 2016 [cited 2020 Jul 8];9:264-8. Available from: http://www.ijournalhs.org/text.asp?2016/9/3/264/196330
| Introduction|| |
Oral drug delivery has been known for decades as the most widely utilized route of administration among all the routes that have been explored for the systemic delivery of drugs through various pharmaceutical products of different dosage forms. The oral route of administration is considered as the most widely accepted route because of its convenience of self-administration, compactness and easy manufacturing accurate dosage, and most importantly the patient compliance. However, the most evident drawback of the oral dosage forms, such as tablets and capsules, is difficulty in swallowing, leading to patients incompliance particularly in case of pediatric and geriatric patients. It has been reported that dysphasia (difficulty in swallowing) is common among all age groups and more specific with pediatric, geriatric population along with institutionalized patients, psychiatric patients and patients with nausea, vomiting, and motion sickness complications. To overcome such problems, fast disintegrating tablets or orally disintegrating tablets (ODTs) have emerged as an alternative dosage forms. These tablets are also called orodispersible, quick disintegrating, mouth dissolving, fast disintegrating, fast dissolving, rapid dissolving, porous, and Rapimelt tablets.
Recently, orally disintegrating tablet technology has been approved by the United States Pharmacopeia (USP), Centre for Drug Evaluation and Research. The US Food and Drug Administration defined orodispersible tablet as “A solid dosage form containing medicinal substances which disintegrates rapidly, usually within a matter of seconds, when placed upon the tongue.” According to the European Pharmacopoeia, these ODTs should disintegrate/dissolve in <3 min.,
- Improved compliance/added convenience
- Ease of administration for patients who are mentally ill, disabled, and noncooperative
- Allows high drug loading
- Ability to provide advantages of liquid medication in the form of solid preparation
- Can be designed to leave minimal or no residue in mouth after administration and also to provide a pleasant mouth feel
- No chewing needed.
Ideal properties of orodispersible tablets
- Require no water for oral administration
- Have a pleasing mouth feel
- Have an acceptable taste masking property
- A harder and less friable
- Leave minimal or no residue in mouth after administration
- Exhibit low sensitivity to environmental conditions (temperature and humidity).
| Materials and Methods|| |
Paroxetine HCl was obtained as gift sample from Cipla Pharmaceuticals Ltd., Mumbai. Crospovidone, sodium starch glycolate, and microcrystalline cellulose were obtained as gift sample from Elegant Pharma, Hubballi; Crystal Pharma, Hubballi.
Formulation of tablet by direct compression method
The drug was mixed with proper portion of superdisintegrant as mentioned in [Table 1]. Care should be taken to confirm the proper mixing of drug and superdisintegrant. Then, other excipients were added. Then, the mixture is passed through sieve (sieve No. 44). Tablet weight and hardness were adjusted to 100 mg and 3–5 kg/cm 2. Finally, the blend is subjected for compression using Rimek tablet punching machine.
|Table 1: Formulation table of paroxetine HCl by direct compression method|
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Formulation of tablet by sublimation method
The basic principle involved in preparing orodispersible tablets by sublimation technique is addition of a volatile salt (camphor) to the tablet components as mentioned in [Table 2]. Two formulations were developed by varying concentration of subliming agent, i.e., camphor (8–10 mg).
Accurately weighed ingredients were sifted through sieve No. 44 and thoroughly mixed for 10 min and magnesium stearate and other ingredients were added to the blend and thoroughly mixed. The tablets were compressed using Rimek tablet punching machine. The compressed tablets were then subjected to sublimation at 60°C for 30 min. The tablets were evaluated for disintegration time and mean tablet weight.,
Evaluation of powder blend
The powder blend obtained by direct compression and sublimation technique was evaluated for angle of repose, bulk density, tapped density, and percentage compressibility.
Angle of repose (θ)
Angle of repose is defined as the maximum angle possible between the surface of a pile of the powder and horizontal plane. The frictional force in a loose powder or granules can be measured by angle of repose.
tan θ = h/r
Where, θ is the angle of repose
h is height of pile
r is radius of the base of pile.
Bulk density and tapped density
Both loose bulk density (LBD) and tapped bulk density (TBD) were determined. A quantity of accurately weighed powder (bulk) from each formula, previously shaken to break any agglomerate formed was introduced into a 25 ml measuring cylinder. After the initial volume was observed, the cylinder was allowed to fall under its own weight onto a hard surface from the height of 2.5 cm at 2 s interval. The taping was continued until no further change in volume was noted. LBD and TBD were calculated using following formula:
LBD = weight of the powder/volume of packing
TBD = weight of the powder/tapped volume of the packaging
Carr's compressibility index
The compressibility index of the powder was determined by Carr's compressibility index.
Evaluation of tablets
Shape and color of tablets
Uncoated tablets were examined under a lens for the shape of the tablet and color was observed by keeping the tablets in light.,
The force required to break a tablet in a diametric compression, i.e., hardness or tablet crushing strength, was measured using Monsanto tablet hardness tester. The hardness was measured in terms kg/cm2.,
Thickness of tablet was measured using vernier calipers. Three tablets were selected at random from each batch and average thickness in mm was reported.
Twenty tablets from each batch were selected at a random and average weight was determined. Then, individual tablets weighed were compared with average weight.
It is the phenomenon whereby tablet surfaces are damaged and/or show evidence of lamination or breakage when subjected to mechanical shock or attrition. The friability of tablets was determined using Roche friabilator. It is expressed in percentage (%). Ten tablets were initially weighed (Winitial) and transferred into friabilator. The friabilator was operated at 25 rpm for 4 min or run up to 100 revolutions. The tablets were weighed again (Wfinal). The percentage friability was then calculated by,
% Friability of tablets <1% is considered acceptable.
In vitro disintegration time
The test was performed using disintegration apparatus. A tablet was placed in each of six tubes of the apparatus and one perforated plastic disc was added to each tube. The time in seconds taken for complete disintegration of the tablet with no palatable mass remaining in the apparatus was noted.
In vitro dispersion time
In vitro dispersion time was measured by dropping a tablet in a 10 ml measuring cylinder containing 6ml buffer solution simulating saliva fluid (pH 6.8).,
In vitro release studies were carried out using tablet USP XXIII type dissolution test apparatus.
Percentage cumulative drug release was plotted against time in minutes to obtain dissolution profile.,,
The purpose of stability testing is to provide evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity, and light and enables recommended storage conditions, retest periods, and shelf lives to be established. ICH specifies the length of study and storage conditions.
- Long-term testing 25°C ± 2°C/60% relative humidity (RH) ±5% for 12 months
- Accelerated testing 40°C ± 2°C/75% RH ±5% for 6 months.
In the present study, stability studies were carried out at 40°C ± 2°C/75% ±5% RH for a specific period up to 28 days for the selected formulations.
| Results and Discussion|| |
Ten formulations of paroxetine HCl were prepared with different concentrations of two individual superdisintegrants crospovidone and sodium starch glycolate. For each formulation, blend of drug and excipients were prepared and evaluated. The formulated blends were evaluated with various parameters as explained earlier. The angle of repose was in the range from 22°78' to 29°35' indicating good flow property. The bulk density and tapped density were in the range of 0.516 ± 0.001–0.566 ± 0.001 g/cc and 0.628 ± 0.002–0.680 ± 0.001 g/cc., The compressibility index and Hauser's ratio were in the range of 12.05 ± 0.01–20.11 ± 0.005 and 11.59–16.79 indicating good flow property. The powder blend was compressed using direct compression and sublimation technique. The compressed tablets were evaluated for physical properties and the results are in permissible limits. The hardness was in the range of 2.96 ± 0.11–3.76 ± 0.25 kg/cm 2. Uniformity of weight was found to be in the range of 98.04 ± 0.6%mg or 102.34 ± 0.98%mg. The friability of all the formulation was within 1%, and they were in the range of 0.04% ±0.002%–0.38% ±0.001% indicating a good mechanical resistance of tablets. The wetting time for all the formulated tablets was in the range of 9.3 ± 0.57–33 ± 1.00 s as shown in [Table 3]. The in vitro drug release for formulations F1, F2, F3, F4, F5, F6, F7, and F8 showed 70.8%, 80.5%, 93.4%, 95.6%, 74.9%, 78.9%, 76%, and 84.6% of drug release, respectively, and S1 and S2 showed 96.7% and 97.5% of drug release as shown in [Figure 1],[Figure 2],[Figure 3]., The disintegration time and drug content of all the formulated tablets were found to be in the range of 9 ± 1.001–30 ± 2.001 s and 95.90%–99.10% as shown in [Table 3]. The thickness was in the range of 3.05 ± 0.023–3.54 ± 0.031 mm as shown in [Table 3].
|Table 3: Wetting time, water absorption ratio, in vitro disintegration time, drug content uniformity, and thickness (F1 to F8 and S1 to S2)|
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| Conclusion|| |
In the present study, two techniques direct compression and sublimation technique were evaluated for their potential for the development of ODTs. From the results obtained, it can be concluded that the sublimation method serves to be better method for this purpose. Two types of superdisintegrants were used, namely, crospovidone and sodium starch glycolate. It can be concluded from the study that F4 formulation and S2 formulation of oral dispersible tablets using crospovidone as a superdisintegrants showed improved solubility, and hence, better disintegration.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]