Home | About PM | Editorial board | Search | Ahead of print | Current Issue | Archives | Instructions | Subscribe | Advertise | Contact us |  Login 
Pharmacognosy Magazine
Search Article 
  
Advanced search 
 


 
  Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 18  |  Issue : 78  |  Page : 314-320  

Exploring cross-linked tragacanth as novel excipient-proof-of-concept


1 Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
2 School of Pharmacy, Management and Science University, Shah Alam, Selangor, Malaysia
3 Department of Pharmaceutics, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, B.G. Nagara, Karnataka, India
4 Department of Pharmaceutical Chemistry, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, B.G. Nagara, Karnataka, India
5 Department of Pharmaceutics, Annamacharya College of Pharmacy, Rajampet, Andhra Pradesh, India
6 Department of Medicine, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia
7 Nanomedicine Lab, Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay (IIT-B), Mumbai, India
8 Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia; Department of Pharmaceutics, Vidya Siri College of Pharmacy, Bengaluru, India
9 Department of Biomedical Sciences, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia

Date of Submission26-Dec-2021
Date of Decision05-Jan-2021
Date of Acceptance12-Jan-2022
Date of Web Publication07-Mar-2022

Correspondence Address:
Anroop B Nair
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, 31982
Saudi Arabia
N Raghavendra Naveen
Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, B.G. Nagar, Mandya - 571 448, Karnataka
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pm.pm_601_21

Rights and Permissions
   Abstract 


Background: Tragacanth, a natural gum, is frequently used as stabilizer for colloidal systems and as a binder in tablets. Materials from natural sources are in increasing demand to solve the current global environmental problems arising from synthesis involving petroleum-based substances. Objectives: In this context, we improved functionality of tragacanth through crosslinking and extended its application for directly compressed fast dissolving systems. Fast dissolving formulations upon settling on the tongue disintegrate promptly and release the medicament, thus making it especially suitable for paediatrics, geriatrics, bedbound, or incapacitated patients. Materials and Methods: Cross-linked tragacanth (CLT) was explored as a potent disintegrant and compared with sodium starch glycolate and Crospovidone for its effect on compressibility and release of metoclopramide hydrochloride from tablets made by direct compression and sublimation method. Formulations made using CLT were optimized for swelling capacity, absorption efficiency, and moisture sorption capacity. Results: The most appropriate controls for linkage of tragacanth were 1:0.4 proportion of tragacanth: Epichlorohydrin, at 105°C temperature for 45 min of reaction. Prepared formulations showed desired disintegration and wetting time. Formulations made using camphor showed porosity because of sublimation and favored rapid disintegration. Based on the drug release study, it is confirmed that formulation with 4% CLT and 20% camphor prepared by sublimation process exhibited highest drug release, i. e. 99.23% within 15 min. Conclusion: This study demonstrates the novel applicability of tragacanth as an effective natural superdisintegrant after cross-linking and provides a sustainable alternative to synthetic superdisintegrants while formulating the fast-disintegrating tablets.

Keywords: Cross-linked tragacanth, metoclopramide hydrochloride, natural disintegrant, orodispersible tablets, tragacanth


How to cite this article:
Nair AB, Fattepur S, Naveen N R, Goudanavar P, Koppuravuri NP, Gowthami B, Telsang M, Osmani RA, Sreeharsha N, Habeebuddin M. Exploring cross-linked tragacanth as novel excipient-proof-of-concept. Phcog Mag 2022;18:314-20

How to cite this URL:
Nair AB, Fattepur S, Naveen N R, Goudanavar P, Koppuravuri NP, Gowthami B, Telsang M, Osmani RA, Sreeharsha N, Habeebuddin M. Exploring cross-linked tragacanth as novel excipient-proof-of-concept. Phcog Mag [serial online] 2022 [cited 2022 Aug 20];18:314-20. Available from: http://www.phcog.com/text.asp?2022/18/78/314/339197



SUMMARY

  • Synthesized CLT was evaluated for swelling capacity, absorption efficiency, and moisture sorption capacity. Based on the drug release profiles using MTH as a model drug, it is concluded that preparation consisting of 4% optimized CLT and 20% camphor showed the highest drug release of 99.23% at the end of 15 mins.




Abbreviations used: CLT: Cross-linked tragacanth; ODT: Orally disintegrating tablets; MTH: Metoclopramide hydrochloride; SSG: Sodium starch glycolate; CP: Crospovidone; SEM: Scanning electron microscopy; FTIR: Fourier transform infrared spectroscopy.


   Introduction Top


Nature derived materials are often more beneficial than the synthetic or artificial because of their attainability, biocompatible, inexpensive, and ecologically sound nature. Herbs are inexhaustible sources for low-cost supportable supplies to the pharmaceuticals.[1] Plant polysaccharides such as tragacanth, comply with the several expectations of pharmaceutical excipients such as availability, nontoxicity, biocompatibility, and hence are extensively used in the formulation development. Furthermore, plant-based excipients are extracted at relatively low cost and can be easily modified chemically to suit-specific needs and impart novel characteristics.[2],[3]

Tragacanth is a natural heteropolysaccharide synthesized by injured plant bark as a result of the defense process to overcome infections and dehydration.[4] Gum tragacanth is extensively used in conventional medicine and the food industry due to the ease of purification, accessibility, inexpensiveness, and their biocompatibility considering their long-term use.[5] It is broadly utilized in line of food, cosmetics, and pharmaceuticals as a protective for colloidal systems, stabilizer, emulsifier, and thickening agent.[6] Despite the use of tragacanth for drug delivery[7] and wound healing, it is not yet explored for orodispersible tablets (ODTs). Solid dosage preparations such as tablets and capsules are majorly chosen formulations owing to their stability, ease in formulation, handling, dosing, and administration in contrast to other dosage forms. Regrettably, the conventional tablets possess some hindrances related to the onset of action and swallowing in geriatric, pediatric, and unconscious patients.[8] To alleviate this drawback and to enhance patient adherence, mouth dissolving or ODT was formulated. ODTs do not require water to swallow as they quickly melt and absorbed in the oral cavity.[2],[9] According to British Pharmacopoeia, ODT is uncoated tablets that are desired to swiftly dissolve in the mouth before swallowing and must have a disintegration time of <3 min. Since the past 20 years, ODT achieved commercial recognition and has been renowned as a substitute for tablets.[10] At present, ODTs are widespread and obtained over the counter for the treatment of various ailments such as fever, cold, and allergies.[11] Quick dissolution of ODT is attributed to the occurrence of a great porous facet in the tablet matrix. Volatile compounds, namely, sublimating agents are employed in tablet manufacturing to enrich the porous nature.[1],[12] that can easily get sublimated out of the finished tablet. Further freeze-drying methods can also be employed to develop highly porous ODT.[13],[14]

Metoclopramide hydrochloride (MTH), a water-soluble potential antiemetic agent, was selected as a model drug for designing ODT. MTH stimulates contractions in the upper gastrointestinal tract, thus enhancing the rate of gastric emptying. It is often used as second-line therapy in the management of hyperemesis gravidarum in pregnant women.[15] Moreover causatively by emergency health-care providers while shifting conscious and spinally immobilized patients. MTH has antagonist effects on D2 ligand at the chemoreceptor trigger zone present in CNS, thus impeding the stimulation of nausea and vomiting. At high doses, serotonin receptor (5-HT3) antagonist effects can provide antiemetic actions. MTH has a gastroprokinetic activity, controlled by cholinergic actions, dopamine antagonist (D2), and serotonin agonist (5-HT4) activities. The self-gastroprokinetic actions may render the antiemetic effects and ameliorate the lower oesophageal sphincter tone.[16]

The present research work is focused on the development of novel excipient by synthesizing cross-linked tragacanth (CLT) and exploring its functionality as a superdisintegrant for making ODT formulations that would enhance the bioavailability of MTH.


   Materials And Methods Top


Materials

MTH was presented by Wallace Pharmaceuticals Pvt. Ltd., Goa. Sodium starch glycolate (SSG) was procured from Micro labs, Bangalore. Tragacanth and cross-povidone (CP) were purchased from Yarrow chemicals, Mumbai. Other ingredients and solvents used were of analytical grade.

Methods

Synthesis of cross-linked tragacanth and optimization of tragacanth cross-linkage

A chemical process was used to synthesize CLT. Dried tragacanth powder and epichlorohydrin were taken in various proportions as 1:0.2, 1:0.5, 1:0.8 [Table 1] and reacted at 60°C to 105°C for a varying period between 45 and 75 min.[17] Since the boiling temperature of epichlorohydrin is 116°C, the reaction temperatures were between 60°C and 105°C. The temperature of the reaction showed a notable impact on the speed of reaction.[18] Optimization was done by evaluating the CLT for swelling capacity, absorption efficacy, and moisture sorption capacity.
Table 1: Optimization parameters in preparing cross-linked tragacanth

Click here to view


P-OH + Cl-CH2-CH-H2C P-O-CH2-CH-CH2-OP

P = Polymer

Fourier transform infrared spectroscopy

Fourier transform infrared spectroscopy (FTIR) spectra of equivalent mixtures (1:1) of MTH and distinct excipients including CLT were conducted to identify the feasible interactivity of drug and excipients through the KBr pellet technique using Perkin–Elmer FTIR series (model-1615) spectrophotometer.[19],[20]

Preparation of metoclopramide hydrochloride oral dissolving tablets

Oral disintegrating tablets of MTH were prepared by direct compression and sublimation methods using CLT, SSG, and CP as per the formula mentioned in [Table 2]. MTH 200 mg tablets each consisting of 10 mg drug were formulated. For all the preparations, mannitol was taken as a diluent. The recommended amount of the drug and excipients were quantified thoroughly and passed through sieve #44 individually, before blending. The contents were then mixed geometrically for 15 min. The resultant mixture was compressed into tablets on single station press machine with 8 mm punches with flat surface.[21],[22] The compression pressure was modified to achieve the tablet hardness in a specified range of 2–4 kg/cm3. The tablets produced by the sublimation process using camphor were subjected to drying [Figure 1] at 60°C in an oven until weights remained unchanged. A total of 15 formulations were prepared using varying concentrations of the selected super disintegrants as tabulated in [Table 2].
Figure 1: Process of sublimation

Click here to view
Table 2: Formulation of Metoclopramide hydrochloride oro-dispersible tablet for optimization of cross-linked tragacanth

Click here to view


Estimation of powder blend (preloading variables)

The powder was evaluated for different flow characteristics such as angle of repose, density indices, Carr's index, and Hausner's ratio.[23]

Postcompression examinations[17]

Hardness

Tablet hardness is the pressure that is essential for breaking a tablet in a specific diametral compression. Erweka Hardness Tester (Erweka, Germany) was utilized in the study. The tester exerts absolute pressure on the tablet. Six tablets were examined and their mean was computed

Friability

The friability (F) was determined using Roche friabilator (ERWEKA, Germany). The weight of 20 tablets was noted individually and subjected for rotation at 25 rpm for 4 min. After dedust tablets were again reweighed. The loss % was quantified. The allowable range of friability is <1%.

Weight variation test

Weight variation test was performed by taking weight of 20 tablets separately, computing the mean weight and compare the independent tablet weight to the mean weight.

In vitro disintegration test

Tablet was kept in a beaker consisting of 20 ml distilled water at 37°C ± 0.5°C. The required time for entire tablet disintegration was determined in triplicate.

Thickness uniformity

The thickness of each tablet crown was estimated by digital vernier calipers. Thickness variation must be <5%.

Water absorption ratio (R)

A double folded tissue paper was kept in a petri plate of 5 cm inner diameter and consisting of 6 ml water. A compressed tablet with 100 mg of CLT was positioned vigilantly on the tissue in the petri plate. The water absorption ratio (R) was calculated based on the formula below:

R = 100 × (Wa – Wb)/Wb

Where “Wb” and “Wa” were tablet weights before and after water absorption, correspondingly. The degree of swelling as measured by the water absorption ratio.

Determination of moisture uptake

Before conducting the test, compressed CLT tablets were held in a desiccator for 1 day to ensure complete film drying. Then, the weight of the CLT tablets was noted and were stored at 75% RH, at ambient temperature for 1 week. Tablets were reweighed, and the percent of weight increase due to moisture absorption was recorded.

Wetting time

The wetting time can be determined by an easy process. A filter paper of 10 cm diameter was positioned in a Petri dish and 1 ml of water-based color amaranth was added. A tablet was cautiously kept on top of the filter paper. The required time for water to get to the tablet superficial facet was recorded.[24] Three estimations were conducted.

Scanning electron microscopy

It was performed to study the exterior facet and internal organization of the formulated tablets. SEM pictures were recorded by Philips XL30 SEM (Eindhoven, The Netherlands). Through surgical scalpel, samples were prepared from the tablet surface and internal sheets. A further sample was boarded on the aluminum stump and sputter deposit-varnished with gold. Photographs were captured at an increasing potential of 10 kV and a magnifying resolution of × 10.[13]

In vitro dissolution studies

USP dissolution test apparatus type 2 paddle (Electrolab TDT-08 L Dissolution testers USP) was employed for the test. A volume of 900 ml phosphate buffer pH 6.8 was taken in a vessel and maintained at 37 ± 0.5°C. The paddle rotation was set to 50 rpm. Samples were drawn at interim of every 5 min, and drug content was estimated by UV Vis spectrophotometrically at a wavelength of 273 nm.[25] Drug concentration was calculated from the calibration curve and denoted as aggregate percent drug dissolved.

Stability studies

This test was conducted by settling the sample instability cabin at 40°C ± 20°C/75% ± 5% RH for 3 months as specified in ICH guidelines. The standardized set was chosen for the stability test. Tablets were tested for disintegration time and in vitro drug release after an interim of 1 month.[26],[27]


   Results And Discussion Top


Nature has provided us a wide variety of ingredients which are biologically active as well as inactive and thus help improve and sustain the health directly or indirectly. With a continuous increasing interest in polymers of herbal origin, the pharmaceutical world has compliance to use most of them in their formulations. Pharmaceutical preparations require a variety of nonactive ingredients in addition to the active drug molecule for variety of purposes such as diluent, binder, thickeners, stabilizer, emulsifier, gelling, coloring, and sweetening. In the recent years, there is a continuous demand for the use of green natural or semi-synthetic ingredients that can be used in place synthetic chemicals.

Drug-excipient interactions studies by Fourier transform infrared spectroscopy

The peak observed for every preparation corresponds with the peak of the drug spectrum. It denotes that the drug and formulation additives used are compatible. The spectra for all formulations are displayed in [Figure 2]. The IR spectrum of the pure MTH shows characteristic peaks at 3396 and 3308 per cm due to –NH and– OH groups correspondingly [Figure 2]a and [Table 3]. The physical mixture of MTH + SSG, MTH + CP, and MTH + CLT, also exhibited similar peaks for the groups mentioned above. This validates the uninterrupted structure of the drug in the formulations. Thus, no interactions were observed between drug and excipients.
Figure 2: Fourier transform infrared spectroscopy spectra of (a) metoclopramide hydrochloride (MTH), (b) Physical mixture of MTH + sodium starch glycolate, (c) MTH + crospovidone and (d) MTH + cross-linked tragacanth

Click here to view
Table 3: Peaks observed in Fourier Transform Infrared Spectroscopy spectrum of pure metoclopramide hydrochloride and physical mixture with super disintegrants

Click here to view


Optimization of preparation of cross-linked tragacanth

CLT was prepared with different ratios of epichlorohydrin, reaction temperatures, and reaction time. Considering the inherent features of tragacanth[Table 4], the standardized conditions for cross-linking were observed as (CLT 14);
Table 4: Evaluation of prepared cross-linked tragacanth

Click here to view


  1. 1:0.4 ratio of tragacanth: Epichlorhydrin
  2. The temperature of 105°C for reaction
  3. The reaction time of 45 min.


Evaluation of the powder blend

The angle of repose (θ) is an attribute of inner abrasion or particle coherence. It is high for cohesive powders and low for noncohesive powders. All preparations exhibited good to allowable flow properties as stipulated by the values of angle of repose (23.18°–28.32°). The angle of repose <30° denotes free-flowing material and >40° with inferior flow characteristics. Carr's index exhibited a value of 20 indicating that the formulated powder mix possesses allowable to good flow behaviour. Powders with less interparticle resistance, exhibited Hausner's ratios around 1.09–1.25, denoting good flow characters. All the preparations were found to have a Hausner's ratio within the specified range [Table 5].
Table 5: Precompression parameters for prepared batches (values are mean of six determinations±standard deviation)

Click here to view


Evaluation of tablets

The tablets prepared were evaluated for the physical and chemical characteristics. The tablets were observed to be within the allowable pharmacopeial range for weight variation and qualified for uniformity of weight. The hardness of the tablets was from 2.8 to 3.5 kg/cm2. For all the preparations, friability (%) was <1 denoting that the tablets were instinctively firm and can resist adversity during transit and operation [Table 6].
Table 6: Postcompression parameters for prepared batches

Click here to view


Wetting dispersion times decreased by increasing both the SSG and CP concentration. Formulation DCT8 and DCT9 prepared by sublimation approach containing CLT exhibited a reduction in wetting and dispersion times compared to the formulation prepared by direct compression method [Figure 3].[28] The same results were obtained for tablets prepared by the sublimation method. It was also found that all sublimated preparations exhibited decreased values of wetting and dispersion times compared to direct compression formulations.
Figure 3: Graph representing a comparison of disintegrating time and wetting time for prepared formulations

Click here to view


The reduction of wetting and dispersion times in all preparations is ascribed perhaps to the existence of super-disintegrant that draw up water and distend resulting in tablets blowout.[27],[29] Further, the camphor present in the tablets formulated by the sublimation process allows the tablet to be porous and promotes the dissemination of the wetting medium, and results in tablet bust. Dispersal time is critical for oral disintegrating tablets which is ideally required to be <1 min. This swift breakdown aids in swallowing and also absorption in the oral cavity and consequently enhances bioavailability.[30] Tablet formulations SCT14 and SCT15 were noted to be favorable as they showed minimum wetting and disintegration time, which make them suitable for use in the oral cavity.

Scanning electron microscopy

Sublimated tablets were evaluated for SEM for the evidence of pores formation [Figure 4]. In sublimated tablets, pores were developed on the evaporation of volatile agent (camphor) leaving tablet core which favors for rapid and fast disintegration.
Figure 4: Scanning electron microscopy studies of sublimated tablets

Click here to view


In vitro dissolution studies

Based on the data of in vitro dissolution test, it was observed that there is a rise in the amount of drug release as the concentration of superdisintegrants increased up to a certain concentration (optimum concentration), regardless of the superdisintegrant used. The maximum drug release for the directly compressed tablets with CLT (4%) was found to be 89.36% at the end of 15 min. The maximum drug release for the sublimated tablets with CLT (4%) was found to be 99.23% at the end of 15 min [Figure 5]a and [Figure 5]b. By changing the preparation method of tablets to sublimation, the dissolution pattern of the tablets prepared by the camphor sublimation method at 20% concentration was observed to be rapid than those prepared by direct compression and sublimation with 10% camphor.[21] This was because of their low hardness and the porous behavior which infiltrates dissolution medium into the tablet pores formed by sublimation of camphor which facilitates quick and complete disintegration. While tablets formulated with SSG showed lesser release than formulations with CP. The rapid disintegration and dissolution of formulations with CLT was due to high swelling power and wicking property compared to SSG and CP.
Figure 5: Comparison of dissolution profiles of formulations prepared by (a) direct compression and (b) sublimation process

Click here to view


Stability studies

No alteration was seen in the physical aspects of SC15 in both the storage circumstances throughout the study period. The dissolution test samples were compared by calculating similarity and dissimilarity factors using the optimized formulation (initial) as a reference to ensure the same release pattern. As required, all the samples showed an excellent similarity profile (>90) concerning the reference formulation [Table 7].
Table 7: Stability studies for selected optimized formulation

Click here to view



   Conclusion Top


Plant-based materials are renewable and can be obtained in a sustainable manner, thus meeting the requirements of constant availability supply of the raw material. CLT was synthesized, and the process was optimized for ratio of reactants and reaction time and temperature. Synthesized CLT was evaluated for swelling capacity, absorption efficiency, and moisture sorption capacity. Considering the inherent features of tragacanth, the standardized conditions for cross-linking were observed as, 1:0.4 proportion of tragacanth: Epichlorohydrin, reaction temperature 105°C for 45 min. Based on the drug release profiles using MTH as a model drug, it is concluded that preparation consisting of 4% optimized CLT and 20% camphor made into ODT by sublimation method showed the highest drug release of 99.23% at the end of 15 min. This study provides a proof-of-concept for the use of natural polysaccharide as a super disintegrant after chemical modification. The easy to scale up platform technology used in the present study can be commercialized and applied to several other oral medications the require rapid onset of action

Plant-based materials are renewable and may be obtained in a sustainable manner therefore fulfill the criterion of consistent availability supply of the raw material. This study provides a proof-of-concept for the use of natural polysaccharide as a super disintegrant following chemical modification. The easy to scale up platform-technology employed in the present work can be commercialized and used to various other oral drugs the require quick onset of action.

Acknowledgments

Authors thank Deanship of Scientific Research at King Faisal University, Al-Ahsa, Saudi Arabia for supporting to the project.

Financial support and sponsorship

This research was funded by the Deanship of Scientific Research at King Faisal University, Al-Ahsa, Saudi Arabia (Nasher Track Grant No. 206112).

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Kumar R, Patil S, Patil MB, Patil SR, Paschapur MS. Isolation and evaluation of disintegrant properties of fenugreek seed mucilage. Int J PharmTech Res 2009;1:982-96.  Back to cited text no. 1
    
2.
Beneke CE, Viljoen AM, Hamman JH. Polymeric plant-derived excipients in drug delivery. Molecules 2009;14:2602-20.  Back to cited text no. 2
    
3.
Adimoolam S, Cindy L. Formulation and In vitro Evaluation Of Diclofenac Sodium In Situ Gelling System By Fenugreek Seed Mucilage 2107;2:88-100.  Back to cited text no. 3
    
4.
Majumdar SH. Comparative success of natural superdisintegrant over synthetic superdisintegrants in fast disintegrating tablets. Asian J Biomed Pharm Sci 2012;2:69.  Back to cited text no. 4
    
5.
Srinivas K, Prakash K, Kiran HR, Prasad PM, Rao ME. Study of Ocimum basilicum and Plantago ovata as disintegrants in the formulation of dispersible tablets. Indian J Pharm Sciences 2003;65:180.  Back to cited text no. 5
    
6.
Mohammadifar MA, Musavi SM, Kiumarsi A, Williams PA. Solution properties of targacanthin (water-soluble part of gum tragacanth exudate from Astragalus gossypinus). Int J Biol Macromol 2006;38:31-9.  Back to cited text no. 6
    
7.
Siahi MR, Barzegar-Jalali M, Monajjemzadeh F, Ghaffari F, Azarmi S. Design and evaluation of 1- and 3-layer matrices of verapamil hydrochloride for sustaining its release. AAPS PharmSciTech 2005;6:E626-32.  Back to cited text no. 7
    
8.
Alam MT, Parvez N, Sharma PK. FDA-approved natural polymers for fast dissolving tablets. J Pharm (Cairo) 2014;2014:952970.  Back to cited text no. 8
    
9.
Hirani JJ, Rathod D, Vadalia K. Orally disintegrating tablets: A review. Trop J Pharm Res 2009;8:161-72.  Back to cited text no. 9
    
10.
Bandari S, Mittapalli RK, Gannu R. Orodispersible tablets: An overview. Asian Journal of Pharmaceutics (AJP): Free full text articles from Asian J Pharm 2014;2.  Back to cited text no. 10
    
11.
Jeevanandham S, Dhachinamoorthi D, Chandra Sekhar K, Muthukumaran M, Sriram N, Joysaruby J. Formulation and evaluation of naproxen sodium orodispersible tablets – A sublimation technique. Asian J Pharm 2010;4. [doi: 10.4103/0973-8398.63985].  Back to cited text no. 11
    
12.
Kumar R, Patil MB, Patil SR, Paschapur MS, Mahalaxmi R. Development and characterization of orodispersible tablets of aceclofenac by sublimation technique. International Journal of PharmTech Research. 2009;1:210-4.  Back to cited text no. 12
    
13.
Corveleyn S, Remon JP. Formulation and production of rapidly disintegrating tablets by lyophilisation using hydrochlorothiazide as a model drug. Int J Pharm 1997;152:215-25.  Back to cited text no. 13
    
14.
Shoukri RA, Ahmed IS, Shamma RN. In vitro and in vivo evaluation of nimesulide lyophilized orally disintegrating tablets. Eur J Pharm Biopharm 2009;73:162-71.  Back to cited text no. 14
    
15.
Surawski RJ, Quinn DK. Metoclopramide and homicidal ideation: A case report and literature review. Psychosomatics 2011;52:403-9.  Back to cited text no. 15
    
16.
Hoover DF, Baker R. P91theimpactintraoperativemetoclopromideantiemeticingastricbypass patients. Surg Obes Relat Dis 2006;2:339.  Back to cited text no. 16
    
17.
Abd Elbary A, Ali AA, Aboud HM. Enhanced dissolution of meloxicam from orodispersible tablets prepared by different methods. Bull Fac Pharm Cairo Univ 2012;50:89-97.  Back to cited text no. 17
    
18.
Gohel MC, Patel SD, Shah NK, Jani GK. Evaluation of synthesized cross-linked tragacanth as a potential disintegrant. Indian J Pharm Sci 1997;59:113.  Back to cited text no. 18
    
19.
Naveen NR, Gopinath C, Kurakula M. Okra-thioglycolic acid conjugate – Synthesis, characterization, and evaluation as a mucoadhesive polymer. Processes 2020;8:316. [doi: 10.3390/pr8030316].  Back to cited text no. 19
    
20.
Naveen NR, Gopinath C, Rao DS. Design expert supported mathematical optimization of repaglinide gastroretentive floating tablets: In vitro and in vivo evaluation. Future J Pharm Sci 2017;3:140-7.  Back to cited text no. 20
    
21.
Elkhodairy KA, Hassan MA, Afifi SA. Formulation and optimization of orodispersible tablets of flutamide. Saudi Pharm J 2014;22:53-61.  Back to cited text no. 21
    
22.
Naveen NR, Nagaraja TS, Bharathi DR, Reddy JN. Formulation Design and In Vitro Evaluation for Stomach Specific Drug Delivery System of Anti Retroviral drug–Acyclovir. Int J Pharm Life Sci 2013;4:2506-10.  Back to cited text no. 22
    
23.
Naveen NR, Gopinath C, Rao DS. Isolation and assessment of natural mucoadhesive agent isolated from Abelmoschus esculents. J Pharm Res 2017;11:438-43.  Back to cited text no. 23
    
24.
Gohel M, Patel M, Amin A, Agrawal R, Dave R, Bariya N. Formulation design and optimization of mouth dissolve tablets of nimesulide using vacuum drying technique. AAPS PharmSciTech 2004;5:e36.  Back to cited text no. 24
    
25.
Pawar H, Varkhade C, Jadhav P, Mehra K. Development and evaluation of orodispersible tablets using a natural polysaccharide isolated from Cassia tora seeds. Integr Med Res 2014;3:91-8.  Back to cited text no. 25
    
26.
Naveen NR, Kurakula M, Gowthami B. Process optimization by response surface methodology for preparation and evaluation of methotrexate loaded chitosan nanoparticles. Mater Today Proc 2020;33:2716-24.  Back to cited text no. 26
    
27.
Kurakula M, Naveen Raghavendra N. Prospection of recent chitosan biomedical trends: Evidence from patent analysis (2009-2020). Int J Biol Macromol 2020;165:1924-38.  Back to cited text no. 27
    
28.
Pabari RM, Ramtoola Z. Effect of a disintegration mechanism on wetting, water absorption, and disintegration time of orodispersible tablets. J Young Pharm 2012;4:157-63.  Back to cited text no. 28
    
29.
Faroongsarng D, Peck GE. The swelling and water uptake of tablets III: Moisture sorption behavior of tablet disintegrants. Drug Dev Ind Pharm 1994;20:779-98.  Back to cited text no. 29
    
30.
Elmeshad AN, El Hagrasy AS. Characterization and optimization of orodispersible mosapride film formulations. AAPS Pharm Sci Tech 2011;12:1384-92.  Back to cited text no. 30
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

Top
   
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
    Materials And Me...
    Results And Disc...
   Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed844    
    Printed43    
    Emailed0    
    PDF Downloaded55    
    Comments [Add]    

Recommend this journal