Formulation and Evaluation of Fast Disslovingtabletsof Doxophylline

FORMULATION AND EVALUATION OF FAST DISSLOVINGTABLETSOF DOXOPHYLLINE

BY

NIRAJ KUMAR GIRI

DEPARTMENT OF PHARMACEUTICS

DISSERTATION PROTOCOL

SUBMITTED TO THE

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE-560041,
KARNATAKA.

UNDER THE GUIDANCE OF

VAZIR ASHFAQ AHAMED

ASST.PROFESSOR

DEPARTMENT OF PHARMACEUTICS

M.M.U. COLLEGE OF PHARMACY

RAMANAGARAM-562159

KARNATAKA

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA, BANGALORE

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / NAME OF THE CANDIDATEAND
ADDRESS (IN BLOCK LETTERS) / NIRAJ KUMAR GIRI
S/O- GAURI SHANKAR GIRI
BIDHYAPATINAGAR, SHREEPUR, WARD NO.-14,BIRGUNJ
DIST.-PARSA,NEPAL.
2. / NAME OF THE INSTITUTION / M.M.U COLLEGE OF PHARMACY
K.K DODDI, RAMADEVARA BETTA ROAD,RAMANAGARAM-562159,
KARNATAKA.
3. /

COURSE OF STUDY AND SUBJECT

/ M. PHARM
PHARMACEUTICS.
4. / DATE OF ADMISSION OF COURSE / 06-10-2011
5. /

TITLE OF TOPIC

/ FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETS OF DOXOPHYLLINE.
6. / BRIEF RESUME OF THE
INTENDED WORK
6.1 Need for the study
6.2 Review of the literature
6.3 Objectives of the study / ENCLOSURE-I
ENCLOSURE-II
ENCLOSURE-III
7. /

MATERIALS AND METHODS

7.1 Source of data
7.2 Method of collection of data
7.3 Does study require any Investigations or interventions to be conducted on patients or Other human or animal? If so, Please describe briefly.
7.4 Has ethical clearance been obtained from your institution in case of 7.3 / ENCLOSURE-IV
ENCLOSURE-V
ENCLOSURE-VI
ENCLOSURE-VII
8. / LIST OF REFERENCES / ENCLOSURE-VIII
9. / SIGNATURE OF CANDIDATE
10. / REMARKS OF GUIDE / Recommended for approval
11. / NAME AND DESIGNATION OF
11.1 Guide
11.2 Signature
11.3 Co guide (if any)
11.4 Signature
11.5 Head of department
11.6 Signature / Mr. VAZIR ASHFAQ AHAMED
ASST.PROFESSOR,
DEPARTMENT OF PHARMACEUTICS,
M.M.U COLLEGE OF PHARMACY,
K.K DODDI, RAMADEVARA BETTA ROAD, RAMANAGARAM-562159,
KARNATAKA.
Not applicable
Not applicable
Mr. VAZIR ASHFAQ AHAMED
ASST.PROFESSOR,
DEPARTMENT OF PHARMACEUTICS,
M.M.U COLLEGE OF PHARMACY,
K.K DODDI, RAMADEVERA BETTA ROAD,RAMANAGARAM-562159,
KARNATAKA.
12. / 12.1 Remarks of the
Chairman and principal
12.2 Signature / SUBMITTED FOR APPROVAL
6. / BRIEF RESUME OF THE INTENDED WORK
ENCLOSURE-I
6.1 Need for the study
A fast dissolving drug delivery system,in most cases,is a tablet which dissolves or disintegrates quickly in oral cavity upon the contact with saliva, resulting in solution or suspension of administeredsolid dosage form that dissolves or disintegrates rapidly in oral cavity.Fast dissolving tablets dosage formsalso known as fast melt, quick melt,orally disintegrating tablets, and orodispersible systems,have the unique property of disintegrating the tablet in mouth in seconds.Recently, the European pharmacopoeia adopted the term orodispersible tablet as a tablet to be placed in mouth where it disperses rapidly before swallowing and which disintegrates in less than 3minutes.11
Asthma is a chronic inflammatory disease, which includes bronchial hyperactivity and bronchospasmcharacterized by hyper responsiveness of tracheo-bronchial smooth muscle to variety of stimuli, resulting in narrowing of air tubes, often accompanied by increased secretions and mucosal edema resulting in breathlessness or dyspnea, wheezing cough, chest congestion and anxiety about being unable to breathe.2
Oral administration is the most widely accepted route of delivery due to its ease of administration, convenience, versatility and most importantly patient compliance. Fast dissolving technologywhich offersquick disintegration and dissolution of tablets, no residue in mouth, requires no water intake, provides a pleasant mouth feel and even allows high drug load.2
Doxophylline ([7-(1,3-dioxolan-2-ylmethyl)theophylline] is a methylxanthine bronchodilatorcharacterized by the presence of adioxolane group in position.Bronchodilator activities of doxophyllinehave been documented in animal studies1-3and in clinical trials involving patients witheither bronchial asthma or chronic obstructivepulmonary disease.Doxophylline activity is mediated, at leastpartly, by the inhibition of phosphodiesteraseenzymes followed by the increase of intracellularconcentrations of cyclic AMP that islikely to cause smooth muscle relaxation.Moreover, it has been suggested that decreasedaffinities toward adenosine A1 andA2 receptors may account for the better safety profile of the drug. Additionally, unliketheophylline, doxophylline did not antagonizecalcium channel blocker receptors and didnot interfere with the influx of calcium intothe cells.12
An attempt is undertaken to formulate fast dissolving tablets of a model bronchodilator drug, Doxophylline with an aim of providing faster onset of action to relieve immediately acute asthmatic attack.
ENCLOSURE II
6.2Review of literature
1.Suresh S, Pandit V, Joshi HP: Fast dissolving tablets of Salbutamol sulphate were prepared by wet granulation process using sublimable components viz.camphor and ammonium bicarbonate .All the formulation containing microcrystalline cellulose and ammonium bicarbonate showed least disintegration time of 5 sec .Magnesium stearate and talc were used as glidant. Thus fast dissolving tablets can be prepared for faster action and which has advantages over conventional dosage forms.1
2.Rangasamy M, Ayyasamy B, Raju S, Gummadevelly S:Fast dissolving tablets of Terbutaline sulfate were prepared by direct compression method. In this method different superdistegrants such as Explotab,Ac-Di-Sol and polyplasdone XL were used in different concentration.Among all of them 5%w/w concentration of polyplasdone superdisintegrant was best formulation for preparation of fast dissolving tablet of terbutaline which release 99.33% of drug.2
3.Shirwaikar A.A, RameshR: Fast disintegrating tablets of Atenolol were prepared by dry granulation method. Three super disintegrants were used i.e, Croscarmellose sodium (Ac-Di-Sol), Crospovidone (polyplasdone XL) and sodium starch glycolate (Explotab) having different concentrations. Drug content of all formulations was found in the range of 97-102%. All the formulations has disintegration time of less than 70 sec. Among the three super disintegration used, Ac-Di-Sol showed the highest efficiency.3
4.Swamy PV, Areefulla SH, Shirsand SB, Gandra S, Prashant B:Orodispersible tablets of Meloxicam were prepared by direct compression method employing combination of two super-disintegrants at a time i.e, sodium starch glycolate-croscarmellose sodium or sodium glycolate- crospovidone.4
5.Patel DM, Patel MM:The fast dissolving tablets of Etoricoxib containing menthol, crospovidone andmannitol were prepared by wet granulation technique. Menthol was sublimed from the granules by exposing the granules to vacuum. A 32 full factorial design was applied to investigate the combined effect of 2 formulation variables: amount of menthol and crospovidone. Sublimation of menthol from tablets resulted in rapid disintegration as compared with the tablets prepared from granules that were exposed to vacuum. The DT and % friability for F1-F9 optimized tablet formulations ranging from 22 to 232 sec and 0.113 % to 0.414 % respectively.5
6.Jain CP,Naruk PS:Fast dissolving tablets of Valsartan were prepared by direct compression method using super disintegranting agent i.e,Ac-Di-Sol,Crospovidone, Sodium starch glycolate.As the concentration of superdisintegrants increased the drug release was also increased .The release rate was found to follow the order:Crospovidone>Ac-Di_Sol>Sodium starch glycolate.So fast dissolving tablets of Valsartan containing crospovidone as superdisintegrants was most acceptable.6
7.Zade PS, Kawtikar PS, Sakarkar DM:Fast dissolving tablets of Tizanidine hydrochloride were prepared by direct compression method.Eudragit E100 was used as taste masking of Tizanidine hydrochloride .The taste masked granules of drug were prepared after incorporating different superdisintegrants such as croscarmellose,crospovidone and sodium starch glycolate in different concentrations. Fast dissolving tablet of Tizanidine hydrochloride was prepared by sublimation method using camphor as sublimating agent.Among both method tablets prepared by using superdisintegration was found to be superior than of sublimation method.7
8.Jeevanandham S, Dhachinamoorthi D, Chandra Sekhar KB, Muthukumaran M, Sriram N, Joysaruby J:Orodispersible tablets of Naproxen sodium were prepared by wet granulation merhod using camphor as subliming agent.Sodium starch glycolate and crosscarmellose were used as superdisintegrants.Mannitol was used as diluents.Sodium saccharine was used as sweeting agent and alcoholic solution of PVP (10%w/v) as binder .Magnesium stearate and talc as flow promoter.The sublimation method shows better disintegration and drug release.The tablets disintegrates within few seconds without need of water.8
9.Raghavendra Rao NG, Patel T, Gandhi S: Fast dissolving tablets of Carbemezepine were prepared by direct compression method using various super disintegrants like croscarmellose sodium, crospovidone indion-414 and sodium starch glycolate to enhance the solubility of the drug, a complex of carbamezepine was prepared with β-cylcodextrin and was compressed into tablets. Microcrystalline cellulose and mannitol were used as diluents. The half life of drug ranges from 18 to 60 hours. In vitro dissolution study was carried out in the USP dissolution test apparatus. The formulation B8, which contains 10% croscarmellose sodium was better because it satisfies all the criteria of fast dissolving tablet.9
10.Sharma S, Gupta GD:Fast dissolving tablets of Promethazine theoclate were prepared by direct compression. Three super disintegrants i.e, Ac-Di-Sol, sodium Starch Glycolate and Crosprovidone were used in different concentrations. 9 formulations were prepared having super disintegrants. The vitro studies of fast dissolving tablets were performed by using type II apparatus as specific in United State Pharmacopoeia at 100 rpm. Absorption of filtered solution was checked by UV spectroscopy (Shimadzu, Japan) and drug content was determined from standard calibration curve. In vitro dissolution studies for f3 confirmed the results, f3 tablet showed good dissolution efficiency and rapid dissolution.10
ENCLOSURE-III
6 6.3 Objectives of the study
1. To select suitable super disintegrant for the preparation of fast dissolving tablets.
2. To formulate Doxophylline fast dissolving tablets.
3. To evaluate physicochemical properties for the prepared formulation.
4. To carry out in-vitrorelease study of tablets.
MATERIALS AND METHODS:
Materials:
Drug : Doxophylline
Excipients:Microcrystalline cellulose powder (MCCP),Starch,PVPK-30,Ac-Di-Sol(Croscamellose),Crospovidone, Sodium Starch Glycolate,Magnesium stearate,Purified Talc, Lactose Monohydrate, Aerosil etc.
Solvent: Water,Ethanol, Chloroform,Isopropyl alcohol,Acetone, Alcohol
Equipments: Digital balance, Mechanical Stirrer, Dissolution apparatus, UV-
spectrophotometer, scanning electron Microscope, differential
scanning calorimeter, Fourier–transformed infrared (FT–IR)
spectrometer.
Methods:
Doxophyllinefast dissolving tablets will be prepared by Wet granulation method or Direct Compression Method.
ENCLOSURE-IV
7.1. Source of Data
1) Review of literature from :
a. Journals : such as
- Indian journal of pharmaceutical sciences.
- Asian journal of pharmaceutical sciences.
- International journal of pharmaceutical research.
- European journal of pharmaceutical sciences.
- International journal of pharmaceutical sciences and Nanotechnology.
b. Internet browsing.
2) Library: M.M.U College of Pharmacy.
3) Laboratory based studies.
ENCLOSURE-V
7.2. Method of Collection of Data
Data on drugs will be collected through literature survey and from physiochemical
database. Extensive preformulation trials would provide the basis for selection of
the suitable excipients and system for final formulation development.
1. Preformulation studies
a) Drug excipient compatibility studies
b) Pharmaceutical evaluation :

• Bulk density
• Tapped density
• True density
• Porosity
• Angle of repose
• Haunser ratio
• Carr’s index
• Moisture content

2. Preparation of tablets:

• Wet granulation Method or Direct compression method.
• Evaluation parameters: weight variation, hardness, friability, disintegration, wetting time & water absorption ratio, content uniformity,in-vitrodissolution study etc.

ENCLOSURE-VI
7.3. Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so, please mention briefly.
-NO-
ENCLOSURE-VII
7.4. Has ethical clearance been obtained from your institution in case of 7.3?
-NOT APPLICABLE-
ENCLOSURE-VIII
LIST OF REFERENCES

1. Suresh S, Pandit V, Joshi HP, Preparation and Evaluation of Mouth Dissolving Tablets of Salbutamol Sulphate, Ind. J Pharm Sci,69,2007,467‐9

1. Manivannam Rangasamy, Balasubramaniam Ayyasamy, Senthilkumar Raju, Design and evaluation of the fast dissolving tablets of Terbutaline Sulphate,Asian J Pharm, 2009;6:215-217

1. Shirwaikar AA, Ramesh R. Fast disintegrating tablets of Atenolol by dry granulation method. Ind. J Pharm Sci 2004: 6:422-426.

1. Swamy PV, Areefulla SH, Shirsand SB, Gandra S, Prashanth B. Orodispersible tablets of meloxicam using disintegrant blends for improved efficacy, Ind. J Pharm Sci 2007;69:836-40

1. Patel DM, Patel MM. Optimization of fast dissolving etoricoxib tablets prepared by sublimation technique, Ind. J Pharm Sci 2008; 70(1): 71-6.

1. Jain CP,Naruk PS.Formulation and evaluation of fast dissolving tablets of valsartan,Int.J of pharm &pharmaceutical sci. 2009;1(1):219-226

1. Zade PS, Kawtikar PS, Sakarkar DM. Formulation, Evalution and Optimization of fast dissolving tablet containing Tizanidine Hydrochloride, Int. J PharmTech Res. 2009;2(1):34-42

1. Jeevanandham S, Dhachinamoorthi D, Chandra Sekhar KB, Muthukumaran M, Sriram N, Joysaruby J. Formulation and evaluation of naproxen sodium orodispersible tablets - A sublimation technique, Asian J Pharm 2010;4:48-51

1. Raghavendra Rao NG, Patel T, Gandhi S. Development and evaluation of carbamazepine fast dissolving tablets prepared with a complex by direct compression technique, Asian J Pharm 2009;3:97-103

1. Sharma S, Gupta GD. Formulation and characterization of fast-dissolving tablet of promethazine theoclate,Asian J Pharm2008;2:70-2

1. Parkash V, Maan S, Deepika, Yadav SK, Hemlata, Jogpal V. Fast disintegrating tablets: Opportunity in drug delivery system, JAdv Pharm Tech Res 2011;2:223-35

1. Bagnato G.F.Tolerability of doxofylline in the maintenance therapy of pediatric patients with bronchial asthma. Eur Rev Med Pharmacol Sci1999; 3: 255-260