Formulation and evaluation of orodispersible tablet of montelukast sodium

 

Siddharth Kumar Sahu, Ajazuddin, Tripti Banjare, Swapnil Gupta, Akansha Bhandarkar, Hemlata Sahu, Shradha Devi Diwedi, Pankaj Sahu, Palak Agrawal, Pooja Yadav, Aditi Bhatt, Kailash Sahu, Deeksha Dewangan, HemlataThapa, Deepika, GyaneshSahu, Mukesh Sharma,

D. K. Tripathi, Amit Alexander *

Rungta College of Pharmaceutical Sciences and Research, Kohka-kurud road, Bhilai, Chhattisgarh, 4900024

 

ABSTRACT:

The objective of the current study was to develop and optimize an orodispersible tablet formulation of montelukast sodium which is an effective drug in the treatment of asthma and allergic disorders. Montelukast sodium is the drug used in treatment of ashthmatic and allergicrhinitis; it is selective leukotrienesreceptor antagonist. Orodispersible tablet is rapid dissolving or disintegrates without water within a few minutes in the oral cavity which may produce rapid onset of action due to the action of superdisintegrants. The orodispersible tablet were prepared by direct compression method using superdisintegrant agent such as croscarmilose sodium, crosspovidone and sodium starch glycolate. Six formulations of superdisintegrants having different concentration were prepared. After examine the angle of repose, bulk density, tapped density, Compressibility index and Hausner’s ratio of powder blend the results were found to be within prescribed limits and indicated good flowing property. The tablets were evaluated for hardness, drug content, friability, weight variation, wetting time and in vitro disintegration time and were found to be satisfactory. Among the formulations tablets of batch F3 and F6 containing co-processed disintegrating agents like croscarmilose: sodium starch glycolate (1:2) and crospovidone: croscarmiloss sodium (1:2) respectively showed superior organoleptic properties along with excellent in-vitro disintegration time and drug release as compare to other formulations. Hence crospovidone is recommended as suitable disintegrant for the preparation of direct compression mouth dissolving tablets of Montelukast sodium.

 

 

 

INTRODUCTION:

Oral delivery route is a useful method of administration of drug when rapid onset of action is desired. It is an effective and safe method of fast disintegrates the tablets¹. Common complaints about difficulty in swallowing tablets in the geriatric, paediatric and travelling patients were may not have vehicle for administration of drug are most need to easy swallowing the drug².

 

This novel type of drug delivery system have some advancement such as fast onset of action, administered without water, instantly releasing the drug, better bioavailability and better patients compliance is preferable for convenient and easy administered dosage form^3-4. According to European pharmacopoeia, these orodispersible tablets should have dissolve or disintegrate in the oral cavity within seconds which gives rapid onset of action with increased bioavailability and good stability5. Montelukast sodium is a chemically (R,E)-2-(1-((1-(3-(2-(7-chloroquinolin-2-yl)vinyl) phenyl)-3-(2-(2-hydroxypropan-2-yl)phenyl) propylthio) methyl) cyclopropyl) acetic acid. It is a selectively and orally active leukotriene (LTD4, LTC4,LTE4) receptor antagonist and it inhibits the cysteinyl leukotriene CysLT1 receptor. This leukotriens are the products of metabolic conversion of arachidonicacid^6-9.That responsible for bronchial constriction and constrictions of smooth muscle and inflammatory processes. Montelukast is the drug of choice in the treatment of asthma in adults and children^10-12. Montelukast sodium is freely soluble in ethanol, methanol, water and insoluble in acetonitrile and oral bioavailability of the 10 mg tablet in adult is upto 60- 64% and in fasting adult is 73%.In this present study, an effort has been made to formulate the orodispersible tablet of montelukast sodium with using the superdisintegrants for enhancing the dissolution rate and hence improvement in compliance^13-15. The superdisintegrants containing crosspovidone, crosscarmilose and sodium starch gycolate with different concentration is made by direct compression method which decreases the disintegration time^16-18. These systems are provide superior profile as potential mucosal absorption as similar as mouth dissolving tablets, rapid disintegrants tablet or quick dissolving tablets¹⁹.

 

MATERIALS AND METHODS:

Crosscarmilose, crospovidine, sodium starch glycolate, Mannitol, Microcrystalline cellulose, Sodium saccharin, Sodium lauryl sulphate (SLS), Talc, and Magnesium stearate were purchased from Loba, Chemie Pvt.  Ltd., India. Montelukast sodium was received as a gift sample from Hetero Drugs, Hyderabad India. All chemicals were used without further purification.

 

Estimation of Montelukast Sodium:

Preparation of buffer solution:

PBS 6.8pH phosphate buffer was prepared by mixing 0.2M potassium dihydrogen phosphate along with 0.2M NaOH, distilled water was added to adjust the volume and make up the volume to 100ml.

 

Preparation of standard stock solution:

The estimation of Montelukast sodium is carried out by preparing stock solution in ethanol solution and further made up dilutions and measures the absorbance at 364.5 nm by using an UV Spectrophotometric method. The method obeyed Beer’s law in the concentration range of 2-10 μg/ml.

 

Preparation of orodispersible tablets by direct compression method

Montelukast sodium orodispersible tablets were prepared by direct compression method by using superdisintegrants like Crospovidone, crosscarmiloss and sodium starch glycolate with different concentration. Mannitolas a diluents, sugar as a sweetening agent

 

 

 

 

 

 

 

Table1. Formulation Design of Different Batches

Ingredients	F1	F2	F3	F4	F5	F6
Montelukast Croscarmiloss Sodium starch glycolate Crospovidone Sugar Talc Magnesium Stearate Mannitol Total	10 5 _ _ 1 2 2 140 180	10 10 _ _ 1 2 2 135 180	10 7.5 7.5 _ 1 2 2 130 180	10 _ _ 5 1 2 2 140 180	10 _ _ 10 1 2 2 135 180	10 7.5 _ 7.5 1 2 2 130 180

 

Evaluation of powder blend:

Micrometrics evaluation of Montelukast sodium

All the ingredients were smoothly ground in a mortar and pestle. Then mesh No.60 is used to pass the all ingredients. Then accurately weight for each specified formulation (table 1) the desired quantity of each ingredient was taken. All micrometric properties of powder blend like Angle of repose, Tapped Density, Bulk Density, % compressibility, Hausner ratio were evaluated as follows and result is given in the table 3.

 

Determination of Angle of Repose:

Angle of repose was determined using funnel method. It is an indication of the frictional forces excited between granule particles. The blend was poured through a funnel that can be raised vertically until a maximum cone height (h) was obtained. Radius of the heap (r) was measured and the angle of repose (q) was calculated using the formula.

 

Tan θ =

Where, θ = the angle of repose, h = height of the heap of the powder, r = radius of the heap of the powder^20-21.

 

Determination of Bulk Density and Tapped Density

Desired amount of the mixed blend (W) was introduced into a 100 ml measuring cylinder and the bulk volume (Vb) was observed as the bulk density. Bulk density was calculated using following formula.

Bulk density = W/Vb

 

The cylinder was allowed to fall under its own weight into a hard surface from the height of 2.5 cm at 2 sec intervals. The tapping was continued until no further change in volume and final volume (Vf) was noted as a tapped density and calculated using the following formula^22-23.

Tapped density = W / Vf

 

Hausner’s Ratio:

It indicates the flow properties of the granules and is measured by the ratio of tapped density to the bulk density²⁴.

 

Hausner’s Ratio = Tapped density/Bulk density

 

Compressibility index (Carr’s Index):

It can be obtained from the bulk and tapped densities.

           Tapped Density – Bulk Density

CI =------------------------------------------ X 100

                    Tapped Density

 

 

Drug-polymer compatibility by FT-IR spectroscopy

A drug-polymer compatibility was analyzed using Fourier Transform Infrared spectrophotometer (Varian 640-IR, USA).The spectra were taken in the wave number region 4000-400 cm⁻¹as KBr pellets of drug (Montelucast Sodium), polymer, physical mixture of drug and polymer and tablet.

 

Compression of Tablets:

The ingredients depicted in (Except Talc and Magnesium stearate) were mixed for sometimes and co ground in a mortar and pestle. Finally talc and Magnesium stearate were added and smoothly mixed homogenously. The mixed blend of drug and excipients was compressed using a multiple punch (Shakti) punching machine to produce round tablets weighing 180mg with a diameter of 8 mm. A minimum of 20 tablets were prepared for each formulation.

 

Evaluation of Montelukast sodium orodispersible tablets:

The thickness, diameter of the tablets was determined using vernier calipers. The hardness of the tablets (n = 6) was determined by using Monsanto hardness tester^25-26.The friability (%) of the tablets was determined using Roche friabilitor. Weight variation test of the tablets was carried out as per the official method²⁷.

 

Weight Variation:

Ten tablets were selected at a random and average weight was calculated. Then individual l tablets were weighed and the individual weight was compared with an average weight²⁸.

                             Average weight – initial weight

% weight variation = --------------------------- × 100

                                       Average weight 

 

Thickness and diameter:

Five tablets were picked from each formulation randomly and thickness and diameter was measured individually. And tablet thickness and diameter was measured by using vernier calliper and it is expressed in mm²⁹.

 

Hardness:

Hardness indicates the ability to resistance to shipping and breakage under condition of storage, transportation and handling before usage depends on its hardness³⁰. The hardness of each batch of tablet was checked by using Monsanto hardness tester. The hardness was measured in terms of kg/cm². 5 tablets of each formulation were chosen randomly and tested for hardness.

 

Friability:

Friability refers to loss in weight of tablets in the containers due to removal of fines from the tablet surface. Friability generally reflects poor cohesion of tablet ingredients³¹. Roche Friabilator was used for the purpose. The % friability was then calculated by the following formula:

 

                                  Initial weight –Final weight

 Percentage friability = ----------------------------X 100

                                               Initial weight

Drug content:

The tablets were tested for their drug content uniformity. At random 20 tablets were weighed and powdered. The powder equivalent to 100 mg was weighed accurately and dissolved in 100ml of 0.5% of Sodium Lauryl Sulphate (SLS) in water. The solution was shaken thoroughly and un-dissolved matter was removed by filtration through Whatmann No.41 filter paper. The sample was then analyzed by taking absorbance against blank at 364.5 nm using UV visible spectrophotometer as per reported procedure³².

 

Wetting time:

Wetting time is closely related to the inner structure of the tablets and to the hydrophilicity of the excipient. It is obvious that pores size becomes smaller and wetting time increases with an increase in compression force or a decrease in porosity. A piece of tissue paper folded double was placed in a Petri plate containing 6ml of water. The tablet was placed on the paper and the time required for water to reach the centre of the upper surface of the tablet was measured in seconds and noted as wetting time³³.

 

In-vitro Disintegration time:

To test the disintegration time of tablets, one tablet was placed in each tube and the basket rack was positioned in a 900ml beaker containing 0.5% of SLS in water at 37°C ± 1°C such that the tablet remains 2.5 cm below the surface of the liquid. The time taken for the complete disintegration of the tablets was noted.

 

In vitro dissolution time:

Dissolution testing of Montelukast sodium fast dissolving tablets was carried out with paddle type in USP dissolution apparatus at rpm 50 and temperature 37±0.5°C in 0.5% SLS in water³⁴. At each specified intervals of time 5 ml sample was withdrawn and replaced by fresh media. The samples were analytically tested to determine the concentration by UV spectroscopy method at wavelength of 364.5 nm.

 

Stability Studies:

Selected formulation were subjected to stability studies as per ICH guidelines at 30°C/ 65 % RH and 40°C / 75% RH for 6 month. Sample were taken and analyzed at 1^st, 3^rd and 6^thmonth as per the stated procedure by Badwaik et al. 2017³⁵.

 

 

 

 

 

 

 

 

RESULTS AND DISCUSSION:

Table2: Calibration curve data of Montelukast sodium

Concentration	Absorbance
2	0.121
4	0.221
6	0.295
8	0.368
10	0.455

 

Fig1 : Standard calibration curve of Montelukast sodium.

 

Calibration curve of montelukast sodium was prepared in 6.8pH phosphate buffer. The slope of the graph was found to be 0.0408 and intercept with -0.0475 with regression coefficient R² = 0.9968.

 

Table3.  Micromeritic Properties of Powder Blend

Code	Bulk density(g/cc)	Tapped density(g/cc)	Carr’s index(%)	Hausner’s ratio	Angle of repose(°)
F1	0.52	0.64	18.75	1.23	24.59
F2	0.5	0.58	13.79	1.16	23.54
F3	0.49	0.55	10.90	1.12	23.34
F4	0.57	0.71	19.71	1.24	25.67
F5	0.55	0.65	15.38	1.18	24.12
F6	0.53	0.59	10.16	1.11	23.67

 

Table4:  Evaluation of Montelukast sodium orodispersible tablets.

Code	Weight variation (mg)	Hardness (kg/cm)	Thickness (mm)	Friability (%)	Drug content (%)	Disintegration time (sec)
F1	179.0±1.6	2.9	3.5	0.69	97.86	36
F2	179.2±2.6	3.12	3.6	0.63	98.52	35
F3	179.5 ±0.8	3.32	3.8	0.57	99.74	29
F4	180.5±1.3	3.15	3.6	0.68	98.30	37
F5	179.3±0.9	3.37	3.5	0.58	96.83	34
F6	180.10±0.4	3.06	3.5	0.54	99.89	30

 

Fig 2: FT-IR spectrum of a) Montelukast sodium, b) Mannitol, c) Montelukast sodium and Mannitol physical mixture, d) Tablet

 

Fig3. Dissolution profile of montelukast sodium

 

Table5: percentage drug release profile.

 

DISCUSSION:

Montelukast sodium tablets were formulated by direct compression method using mannitol, Magnesium stearate, Talc, superdisintegrants croscarmiloss and crosprovidone for developing orodispersible dosage form. The granules were subjected to various preformulation study tests before compression (Table no. 3). The angle of repose from formulation F1 to F6 varied between 23.34to 25.67 showings very free flowing property. The bulk density varied from 0.49 to 0.57 while tapped density ranged from 0.55 to 0.71 both showing good flow ability of powder blends. Carr’s index ranged between 10.16-19.71 and Hausner’s ratio and 1.11-1.24 respectively which also describes good flow property of powders. The Drug polymer compatibility of tablet was assessed by FT-IR spectroscopy and result revelled that characteristics peaks of drug was also present in same wave number in physical mixture and also tablet formulation. This conforms the chemical stability of Montelukast sodium in formulated oral dispersible tablets.

 

The punched tablets of different formulation were also subjected to several evaluation parameters like tablet weight variation, assay, hardness, friability, dissolution study, etc. which is shown in table no. 4. All the tablets passed weight variation test as all of them weighed within given pharmacopoeias limits. The hardness of tablets ranged between 2.9 to 3.37 which indicated good mechanical strength. And ability to withstand physical pressure and stress. The friability was between 0.54 to 0.69 which is within limits and shows good resistance of tablets to mechanical stress. The percent drug content of tablets was within permissible limits i.e. 96.83% to 99.89% (Table 4).

 

Among all the formulations formulation F6 (containing co-processed disintegrating agent) was found to have better release profile when compared to others. The formulation F6 showed NLT 99.89% release in 7minute in accordance with USP dissolution criteria for orodispersible tablet. As concentration of disintegrant increases, increases the drug release.The cumulative percentage of the drug released for formulation F6 showed better drug release (99.89%) within7 min, indicates good bioavilability of the drug from the formulation. Stability study data showed selected formulation (F6) showed no significant variation in the disintegration, friability, hardness and in-vitro drug release.

 

CONCLUSION:

The overall study was done to formulate and evaluated Montelukast sodium orodispersible tablet using different superdisintegration agent and the present study showed that it can be easily formulated without drug polymer incompatability using direct compression technique for fast release, improved bioavailability, patient compliance with effective therapy.

 

All the formulations showed acceptable release among which F6 was best selected out. The study revealed that crosscarmiloss and cros-providone can be used in different ratio for a better disintegration profile. More the concentration of super disintegration agent better in release profile was observed. Thus, it is well understood that drug loaded oral dispersible tablet was stable and shows better drug release profile.

 

ACKNOWLEDGMENT:

Authors want to acknowledge the facilities provided by the Rungta College of Pharmaceutical Sciences and Research, Kohka, Kurud Road, Bhilai, Chhattisgarh, India. The authors also wants to acknowledge Chhattisgarh Council of Science and Technology (CGCOST) for providing financial assistance under mini research project (MRP) vide letter no. 1124/CCOST/MRP/2015; Dated: September 4, 2015 and 1115/CCOST/MRP/2015; Dated: September 4, 2015.

 

REFERENCE:

1.        Chhajed M, Tiwari D. Formulation Development and Evaluation of Montelukast Sodium Orodispersible Tablets. International Journal for Pharmaceutical Research Scholars. 2012;1: 127-139.

2.        Rama Rao N, Chowdary KPR. Improvement of dissolution rates bioavailability of Piroxicam with pre-gelatinized starch. Indian Journal of Pharmaceutical Sciences. 2001; 63: 36-40.

3.        Chowdary KPR, Hymavathy R. Formulation and dissolution rates studies on dispersible tablets of Ibuprofen. Indian Journal of Pharmaceutical Sciences. 2000; 63 (2):213-216.

4.        Alexander A, Ajazuddin, Khan J, Saraf S, Saraf S. Polyethylene glycol (PEG)–Poly(N-isopropylacrylamide) (PNIPAAm) based thermosensitive injectable hydrogels for biomedical applications. European Journal of Pharmaceutics and Biopharmaceutics. 2014; 88 (3): 575-585.

5.        Badwaik HR, Sakure K, Alexander A, Ajazuddin, Dhongade H, Tripathi DK. Synthesis and characterization of poly (acryalamide) grafted carboxymethyl xanthan gum copolymer. International Journal of Biological Macromolecules. 2016; 85: 361-369.

6.        Giri TK., Choudhary C, Alexander A, Ajazuddin, Badwaik H, Tripathy M, Tripathi DK. Sustained Release of Diltiazem Hydrochloride from Cross-linked Biodegradable IPN Hydrogel Beads of Pectin and Modified Xanthan Gum. Indian Journal of Pharmaceutical Sciences. 2013; 75(6): 619-742.

7.        Vyas A, Saraf S, Saraf S, Encapsulation of cyclodextrin complexed simvastatin in chitosan nanocarriers: A novel technique for oral delivery. Journal of Inclusion Phenomena and Macrocyclic Chemistry. 2010; 66 (3-4): 251-259.

8.        Giri TK., Verma S, Alexander A, Ajazuddin, Badwaik H, Tripathy DK. Prospective and New Findings of Hydroxypropyl Methylcellulose (HPMC) as a Potential Carrier for Gastrorententive Drug Delivery Systems. Drug Delivery Letters. 2012; 2: 98-107.

9.        Giri TK, Tandan HK, Choudhary C, Ajazuddin, Alexander A, Badwaik H, Tripathi DK.In-Vitro Evaluation Of Commercially Available Sustained Release Capsule Containing Diltiazem Hydrochloride. International Journal of Pharmacy and Pharmaceutical Sciences.2012; 4(3):523-526.

10.     Giri TK, Barwey N, Verma S, Alexander A, Ajazuddin, Badwaik H, Tripathi DK. Comparative Assessment of the Quality Measurement of Some Commercially Available Paracetamol Tablets. International Journal of Pharmaceutical Sciences Review and Research. 2012; 14(2): 42‐46.

11.     Giri TK, Parveen N, Thakur D, Alexander A, Ajazuddin, Badwaik H, Tripathi DK. In vitro Evaluation of Commercially Available Enteric Coated Tablet Containing Diclofenac Sodium. International Journal of Research in Pharmaceutical and Biomedical Sciences.2012; 3(2): 875-881.

12.     Singh D, Singh M, Saraf S, Dixit VK, Saraf S. Optimization and Characterization of Gentamicin Loaded Chitosan Microspheres for Effective Wound Healing. Indian Journal of  Pharmaceutical Education and Research. 2010; 44 (2): 171-182

13.     Alexander A, Dwivedi S, Ajazuddin, Giri TK, Saraf S, Saraf S, Tripathi DK.. Approaches for breaking the barriers of drug permeation through transdermal drug delivery. Journal of Controlled Release. 2012; 164 (1): 26-40.

14.     Ajazuddin, Saraf S, Applications of novel drug delivery system for herbal formulations. Fitoterapia. 2010; 81 (7): 680-689.

15.     Badwaik HR, Giri TK, Nakhate KT, Tripathi DK. Xanthan gum and its derivatives as a potential bio-polymeric carrier for drug delivery system. Current Drug Delivery. 2013; 10(5):587-600.

16.     Sahu S, Saraf S, Kaur CD, Saraf S. Biocompatible Nanoparticles for Sustained Topical Delivery of Anticancer Phytoconstituent Quercetin. Pakistan Journal of Biological Sciences. 2013; 16: 601-609.

17.     Ajazuddin, Alexander A, Khan J, Giri TK, Tripathi DK, Saraf S, Saraf S. Advancement in stimuli triggered in situ gelling delivery for local and systemic route. Expert Opinion on Drug Delivery. 2012; 9 (12): 1573-1592.

18.     Badwaik HR, Thakur D, Sakure K, Giri TK, Nakhate KT, Tripathi DK. Microwave Assisted Synthesis of Polyacrylamide Grafted Guar Gum and its Application as Flocculent for Waste Water Treatment. Research Journal of Pharmacy and Technology. 2014; 7(4): 401-407.

19.     Giri TK, Thakur D, Alexander A, Ajazuddin, Badwaik H, Tripathi DK. Alginate based Hydrogel as a Potential Biopolymeric Carrier for Drug Delivery and Cell Delivery Systems: Present Status and Applications. Current Drug Delivery. 2012; 9(6): 539-555.

20.     Badwaik HR, Sakure K, Nakhate KT, Dhongde H, Kashayap P, Tripathi DK. Microwave Assisted Eco-Friendly Synthesis, Characterization and in vitro Release Behavior of Carboxymethyl Xanthan Gum. Current Microwave Chemistry. 2016; 3(3): 203-211.

21.     Giri TK, Sahu R, Kumar K, Alexander A, Ajazuddin, Badwaik H, Tripathi DK.In-vitro quality control measurement of some commercially available sustained release tablet containing diclofenac sodium. Research Journal of Pharmacy and Technology. 2012; 5(5): 687-690.

22.     Nagori K, Singh MK, Alexander A, Kumar T, Dewangan D, Badwaik H, Tripathi DK. Piper betle L.: A review on its ethnobotany, phytochemistry, pharmacological profile and profiling by new hyphenated technique DART-MS (Direct Analysis in Real Time Mass Spectrometry). Journal of Pharmacy Research. 2011;4(9):2991-2997.

23.     Alexander A, Ajazuddin, Patel RJ, Saraf  S, Saraf S. Recent expansion of pharmaceutical nanotechnologies and targeting strategies in the field of phytopharmaceuticals for the delivery of herbal extracts and bioactives. Journal of Controlled Release. 2016; 241:110-124. 

24.     Giri TK, Badwaik H, Alexander A, Tripathi DK.  Solubility enhancement of ibuprofen in the presence of hydrophilic polymer and surfactant. International journal of applied biology and pharmaceutical technology. 2010; 1(2): 793-800.

25.     Jeswani G, Alexander A, Saraf S, Saraf S, Qureshi A, Ajazuddin. Recent approaches for reducing hemolytic activity of chemotherapeutic agents. Journal of Controlled Release. 2015; 211:10-21.

26.     Vinay Sagar Verma, Kalyani Sakure, Hemant R. Badwaik. Xanthan Gum a Versatile Biopolymer: Current Status and Future Prospectus in Hydro Gel Drug Delivery. Current Chemical Biology. 2017; 11, 10-20.

27.     Giri TK, Verma S, Alexander A, Ajazuddin, Badwaik H, Tripathy M, Tripathi DK. Crosslinked biodegradable alginate hydrogel floating beads for stomach Site specific controlled delivery of Metronidazole. FARMACIA. 2013; 61(3): 533-550.

28.     Giri TK, Thakur D, Alexander A, Ajazuddin, Badwaik H, Tripathy M, Tripathi DK. Biodegradable IPN hydrogel beads of pectin and grafted alginate for controlled delivery of diclofenac sodium. Journal of Materials Science: Materials in Medicine. 2013; 24: 1179–1190.

29.     Ashawat MS, Shailendra S, Swarnlata S. Preparation and characterization of herbal creams for improvement of skin viscoelastic properties. International Journal of Cosmetic Science. 2008; 30 (3): 183-93.

30.     Alexander A, Saraf S, Saraf S. Understanding the role of poloxamer 407 based thermoreversible in situ gelling hydrogel for delivery of PEGylated melphalan conjugate. Current Drug Delivery. 2016; 13 (4): 621-630.

31.     Giri TK, Kumar K, Alexander A, Ajazuddin, Badwaik H, Tripathy M, Tripathi DK.. Novel controlled release solid dispersion for the delivery of diclofenac sodium. Current Drug Delivery, 2013; 10(4), 435-443.

32.     Singh MK, Nagori K, Badwaik H, Pandey A, Sawarkar HA, Chawla J. Potential Antileprotic Herbal Drugs: A Comparative Review of Marketed Products. Journal of Pharmacy Research. 2011; 4(6): 1875-1876.

33.     Badwaik H, Singh MK, Thakur D, Giri TK, Tripathi DK. The Botany, Chemistry, Pharmacological and Therapeutic Application of Oxalis Corniculata Linn– A Review.  International Journal of Phytomedicine. 2011; 3(1): 01-08.

34.     Giri TK, Verma D, Badwaik HR. Effect of aluminium chloride concentration on diltiazem hydrochloride release from pH-sentive hydrogel beads composed of hydrolyzed grafted k-carrageenan and sodium alginate. Current Chemical Biology. 2017; 11: 44-49.

35.     Badwaik HR, Sakure K, Nakhate KT, Kashayap P, Dhongade H, Alexander A, Ajazuddin, Tripathi DK. Effect of Ca²⁺ ion on the release of diltiazem hydrochloride from matrix tablets of carboxymethyl xanthan gum graft polyacrylamide , International  Journal  of  Biological  Macromolecules. 2017; 94: 691-697.

 

 

 

 

 

Received on 16.08.2017            Modified on 22.09.2017

Accepted on 01.12.2017         © RJPT All right reserved