Download Enhancing Solubility And Dissolution Rate of A Poorly

Development and evaluation of orodispersible tablets of a selected atypical antipsycotic agent using a Novel Co-Grinding solid diperssion Technique.
M.Pharm. Dissertation Protocol Submitted to the
Rajiv Gandhi University of Health Sciences,
Karnataka, Bangalore.
By
Mr. Aditya V. Korachagaon B.Pharm
Under the guidance of
Shri. J.S. Patil M.Pharm (P hD)
Assistant Professor
Department of Pharmaceutics
B.L.D.E.A’s College of Pharmacy, Bijapur-586103
2009-2010
Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1.
2.
Name of the Candidate and
Address
(In block letters)
Name of the Institution
Mr. ADITYA. V. KORACHAGAON
B.L.D.E.A’s College of Pharmacy, Bijapur586 103
3.
Course of study and subject
M.Pharm in Pharmaceutics
4.
Date of admission to Course
15-06-2009
5.
Title of the Topic
Development
orodispersible
and
tablets
evaluation
of
a
of
selected
atypical anti-psycotic agent using a Novel
Co-Grinding solid diperssion Technique
6.
7.
Brief resume of the intended work :
6.1 Need for the study
Enclosure-I
6.2 Review of literature
Enclosure-II
6.3 Objectives of the study
Enclosure-III
Material and Methods :
7.1 Source of data
: Enclosure-IV
7.2 Method of collection of data (including sampling procedure, if any)
: Enclosure-IV
7.3 Does the study require any investigations or interventions to be conducted
on patients or other humans or animals? If so, please describe briefly.
: No
7.4
Has ethical clearance been obtained from your institution in case of 7.3
: No
8.
List of References (about 4-6)
9.
Signature of candidate
: Enclosure-V
2
10.
Remarks of the guide
11.
Name & Designation of
(in block letters)
12.
: Enclosure-VI
11.1
Guide
11.2
Signature
11.3
Co-Guide (if any)
---
11.4
Signature
---
11.5
Head of Department
11.6
Signature
12.1
Remarks of the chairman & principal: This study can be carried out in our
laboratory
12.2
Signature
Shri. J S. PATIL
Assistant Professor
Department of Pharmaceutics
B.L.D.E.A’s College of Pharmacy, BIJAPUR586 103
3
Enclosure-I
6) Brief resume of the intended work
6.1. Need for the study
The effort to improve dissolution and solubility of poorly and practically water
insoluble drugs remains one of the most challenging tasks in drug development. Several
methods have been introduced to increase dissolution rate and thereby oral absorption and
bioavailability of such drugs1. Among various approaches solid dispersion has shown
promising results in improving solubility, wettability, dissolution rate of drug and
subsequently its bioavailablity2 .Co-grinding is one of the solid dispersion techniques which
is superior to other approaches from economical as well as environmental stand points, in
that unlike similar methods it does not require any toxic organic solvents3.
With the increase in the average human life span, drug administration for elderly
patients has become more important.
4
The major problem faced by many patients with
conventional dosage forms is diffcult in swallowing. This problem is more apparent when
drinking water is not easily available to the patient taking medication. Hence, patient may not
comply with prescription, which results in high incidence of ineffective therapy.
5
The fast
dissolving drug delivery system is rapidly gaining acceptance as it offers patient compliance
and better bioavailability than conventional tablets.6,7
Paliperidone/ziprasidone is a newer atypical anti-psycotic drug used in the treatment
of schizophrenia, which is an ongoing mental disease. Frequent relapses occur in about 55%
of schizophrenia patients8, mostly because of medication non-compliance as it depends
upon type of dosage form used. The above said drugs are practically insoluble in water and
also have solubility limited bio-availability (60%).9
There is no reported literature on mouth dissolvingtablet of this drug, thus there is an
obvious need for development of orodispersiable tablets of the above mentioned drug to
overcome patient non-compliance. Hence prior to its formulation as mouth disintegrating
tablets, it is planned to improve its solubility by co-grinding solid dispersion technique.
4
ENCLOSURE-II
6.2. Review of literature
1. Mohammad Barzegar et al., have developed solid depression of carbamazepine via
co-grinding
solid
dispersion
method
using
crospovidone
and
hydrovypropylmethylcellulose as the carriers. The preparations shown high
dissolution profile with both the polymers when compared to their respective physical
mixtures.10
2. Gohel M et al., have developed fast dissolving tablets of nimesulide using camphor,
lactose and crospovidone as sublimating and superdisintergrating agents. The
systematic multiple regression analysis results revieled that the low percentage of
camphor and high percentage of crospovidone shown a better fast dissolving profile.11
3. Sharma S et al., have reported the fast-dissolving tablets of promethazine theoclate by
direct-compression method after incorporating superdisintegrants Ac-Di-Sol, Sodium
Starch Glycolate, and Crospovidone in different concentrations. Tablets containing
Ac- Di- Sol showed superior organoleptic properties, along with excellent in vitro and
in vivo dispersion time and drug release, as compared to other formulations. 12
4. Godge RK et al., have prepared fast dissolving tablets of Tizanidine hydrochloride by
direct compression method using Sodium Starch Glycolate, Ac-Di-Sol, and ndion 414
as a super disintegrants, and controlled tablets without any super disintegrant. All
tablets containing super disintegrants shows release of drug more than 95% within
10 minutes and controlled tablet shows release of drug after 30 minutes. Tablets
containing Indion 414 as a super disintegrant shows better result compare to others.
Result also shows that as the concentration of superdisintegrant increases
percentage release also increases. 13
5. Zade PS et al., have prepared fast dissolving tablet of Tizanidine Hydrochloride using
Eudragit E 100 as a taste masking agent. The tablet was prepared with three super
disintegrants
e.g.
sodium
starch
glycolate,
crosscarmellose
sodium
and
crospovidone. The disintegration in oral cavity was also tested and was found to be
22 sec. Other tablets were prepared by using camphor as sublimating agent. It was
concluded that tablets prepared by addition of superdisintegrant has less
disintegration time than those prepared by sublimation method. 14
5
6. ENCLOSURE-III
6.3. Objectives of the study
The present work is planned with the following objectives.
1. To prepare solid dispersion of Paliperidone/ziprasidone by a novel co-grinding
technique.
2. To evaluate the solid dispersions for phsiochemical properties such as aqueous
solublitry and partition co-efficient & also to study in vitro drug release profile.
3. To characterize the formulations for thermal behaviour by Differnsial Scanning
Calorimetry(DSC), Crystalitnity by x-ray defractography (XRD).
4. To study the drug-excipint comptablity by fourier transform infrared spectroscopy.
5. To formulate a orodisperssible tablets dosage form for the optimized solid dispersion
formulations and their through evaluation.
6. To carry out the in vitro drug release study for a tablet dosage form with the intention
of evaluating the influence of co-grinding techniques and super-disintegrants on fast
disintegration profile.
7. To carry out the stability studies on the prepared formulations as per ICH guidelines.
6
ENCLOSURE-IV
7) MATERIALS AND METHODS
7.1. Source of data
The data will be collected by performing various laboratory experiments, referring
journals, text books and other literature.
7.2. Method of collection of data
The whole data is planned to collect from laboratory experiments which includes the
following,
1) The solid dispersions of drug and exciopents will be prepared by a novel co-grinding
technique using a ball-mill.
2) The formulations will be characterized by Differential scanning calorimetry (DSC),
Infrared Spectroscopy (FTIR), x-ray Diffraction Studies (XRD), and data will be
collected.
3) The solid disperssoin will be converted into orodisperssible tablet dosage forms using
various super-disintegrants and evaluation of tablets.
4) The influence of excipients on the drug release will be studied by conducting
dissolution experiments and data will be collected.
5) The stability studies of the formulations will be carried out as per ICH guidelines and
data will be collected.
7
ENCLOSURE-V
8) List of References
1. Kiran T, Nalini S, Ramakrishna S, Sadanandam M. 2009 “Surface Solid dispersion of
glimepiride for enhancement of dissolution rate”. Int. J. Pharm. Tech.Res. 1: 822-831.
2. Serajuddin A.T.M., 1999 “Solid dispersion of poorly water soluble drugs: Early
promises, subsequent problems and recent breakthroughs”. J. Pharm.Sci, 88:10581066.
3. Friedrich H., Nada A., Bodmeier R. 2005 “ Solid state and dissolution rate
characterization of co-ground mixtures of nifedipine and hydrophilic carriers”. Drug
Dev. Ind. Pharm, 31: 719-728.
4. Kaushik D, Dureja H, Saini TR. 2004 “Mouth dissolving tablets: A review. Ind. Drugs.
41: 503-508.
5. Seager H. 1998 “Drug delivery product and zydis fast dissolving dosage forms. J
Pharm Pharmacol. 50: 375-382.
6. Indurwede H.N, Rajyaguru T.H, Nakhat P.D. 2002 “Novel approach-fast dissolving
tablets”. Ind. Drugs. 39:405-409.
7. Kuchekar B.S., Badhan A.C., Mahajan H.S. 2003 “Mouth dissolving tablet:A novel
drug delivery system. Pharma Times. 35:7-14.
8. Deshmukh S.S., Potnis V.V., Mahaparale P.R., Kasture P.V., Gharge V.S. 2009
“Development
and
evaluation
of
ziprasidone
hydocholride
fast
dissintegratinf/dissolving tablets using complexsation techniques”. Ind. J Pharm Educ
Res. 43:300-307.
9. Loftsson T, Brewster M.E., Massom M. 2004 “Role of cyclo dextrins in improving oral
drug delivery”. Am. J. Drug. Deliv. 2:1-15.
10. Mohammad Barzegar J. et al., 2007 “ Enhancing dissolution rate of carbamazepine
via co-grinding with crospovidone and hydroxypropylmethylcellulose”. Iran. J. Pharm.
Res, 6:159-165.
11. Gohel M, Patel M, Amin A, Agrawal R, Dave R, Bariyal N. 2004 “Formulation
design and optimization of mouth dissolve tablets of nimesulide using vaccum drying
technique”. AAPS PharmSciTech. 5 (3) Article 36.
12. Sharma S, Gupta G.D. 2008 “Formulation and characterization of fast dissolving
tablets of promethazine theoclate”. Asian J Pharm. 2:70-72.
13. Godge K.R., Kendre P.N., Giri M.A., Zama S.M., Lateef S.N. 2009 “Formulation and
in-vitro evaluation of fast dissolving/disintegrating tablets of tizanidine hydrochloride.
Res J Pharm Dosage Forms Tech. 1:55-58.
14. Zade P.S., Kawtikar P.S., Sakarkar D.M. 2009 “Formulation, evaluation and
optimization of fast dissolving tablet containing tizanidine hydrochloride”. Int J
PharmTech Res. 1:34-42.
8
ENCLOSURE-VI
10) Remarks of the Guide
The present work is aimed to develop and evaluate a novel orodispersiable tablet
dosage form for Paliperidone/ziprasidone is a newer atypical anti-psycotic drug used in the
treatment of schizophrenia, which is an ongoing mental disease. Frequent relapses occur in
about 55% of schizophrenia patients, mostly because of medication non-compliance as it
depends upon type of dosage form used. The above said drugs are practically insoluble in
water and also have solubility limited bio-availability (60%).
Thus there is an obvious need for development of orodispersiable tablets of the
above mentioned drug to overcome patient non-compliance. Hence prior to its formulation as
mouth disintegrating tablets, it is planned to improve its solubility by co-grinding solid
dispersion technique.
J S PATIL,M.Pharm.(P hD)
Research Guide
9