RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA.

ANNNEXURE II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1Name and address of candidate

Mr. Sharma Shrikant Mahesh21, Ganesh Society,Near Jijamata Chowk, Talegaon Dabhade Pune : 410506

2 Name of institution

R R COLLEGE OF PHARMACY.Hesaraghatta Main Road, Chikkabanavara Post,Bangalore-560090

3Course of study and subject

Master of Pharmacy(Pharmaceutics)

4 Date of admission 8th NOVEMBER 2010

5 Title of the project“Formulation and Evaluation of Fast Disintegrating Tablets of Loratadine by Sublimation Technique”

6 BRIEF RESUME OF THE INTENDED WORK:

6.1 NEED FOR THE STUDY:

The need of the study was to develop fast disintegrating tablets of Loratidine other

than the patented process, like using sublimation technique. Loratidine is available in

market, marketed under the name of Clartin which is also a fast disintegrating tablet. Clartin

is formulated by a patented process named Zydis which was innovated by R.P. Scherer,

Inc.1, 2, 4 The drawback of this technology is that it requires number of ingredients and is a

sophisticated process and unnecessary rise in cost occurs due to the patented process.

The various individual techniques have their own advantages and disadvantages.31 An

improvisation of the technique can be done by considering the drug properties and using

combination of various techniques in order to develop a new innovative technique which

can override the limitations of each other.

Sublimation technique is an easy and an economic technique for the formulation of

fast disintegrating tablets.1, 2 Superdisindegrants help to disintegrate the tablets rapidly and

cause the dissolution of drug at a faster rate.8 Both techniques can be helpful to formulate

new fast disintegrating tablets. The fast disintegrating tablets must have a pleasing mouth

feel but most of them fail because of the incorporation of microcrystalline cellulose. Use of

mannitol can overcome the drawback mentioned above as it is soluble in saliva and increase

more patient compliance.5, 29

The disintegration of tablets takes place in various steps. The main character required

by the tablet is the requirement of pores, as water enters the pores, it causing swelling and

disintegration.33

The pores in a tablet can be increased by using sublimation technique. A subliming

material like menthol is incorporated into formula and tablet is punched after this the tablet

is kept for sublimation. After sublimation of menthol the place becomes vacant and leads to

formation of pores.

Loratidine is sparingly soluble in water.34 It is freely soluble at pH 1.5 to 2. Increase

in the pH drastically changes the solubility of the drug. Loratidine is classified as the Class

II according to the Biopharmaceutical Classification of Drugs which means sparingly

soluble and highly permeable.19

As there is decrease in solubility when there is rise in pH the fast disintegrating

tablet can be helpful as it would release the drug from tablet within few seconds rather than

conventional tablet which requires 15 minutes.8 So even reduction in gastric transit time

may not cause significant effect on the absorption.13 The incorporation of superdisintegrant

like crospovidone is helpful to increase the solubility of the drug.16

Loratidine is a second generation anti histaminic having no sedative effects.35

Loratidine is a long acting tricyclic peripherally acting histamine antagonist with selective

H1 receptor histamine antagonist activity. It rapidly undergoes first pass metabolism and

converted to its active metabolite desloratidine.21 Receptor binding data indicate that a

concentration a concentration of 2 – 3 ng/ml (7 nano molar) desloratidine shows significant

interaction with human histamine H1 receptor.32 Desloratidine inhibited histamine release

from human mast cells in-vitro.21 Desloratidine and hydroxydesloratidine are approximately

82 % to 87 % and 85 % to 90 % bound to plasma proteins.34 A hypsodiasis condition have

been reported when administered during pregnancy.20

It is mostly used in the allergic rhinitis, hay fever, utricaria and also used as the

over the counter antihistamine agent.35

6.2 REVIEW OF LITERATURE:

K Kathiresan et al.,12 developed a Loratadine chewable tablets. Administration of

Loratadine through oral route is a challenge in children, who have not yet learned to

swallow tablets. In this research five batches of Loratadine chewable tablet dosage form at

the dose of 5 mg was formulated and evaluated. Results showed that thickness, weight

variation, friability, hardness, and content uniformity of all five formulations were within

the acceptance limits. But in the in-vitro dissolution study, formulation 1, 2 and 5

demonstrated better cumulative drug release than formulation 3 and 4. However,

cumulative drug release of formulation 5 was comparable with innovator than formulation 1

and 2. Three month stability study of formulation 5 revealed that there were no significant

change in physical parameters, drug content and dissolution profile. Hence the research

concludes that Loratadine chewable tablets formulated using Avicel CE 15 and starch paste

(Formulation 5) showed better characteristics of chewable table.

Sreˇco D. Škapin and Egon Matijevi´c.,23 developed colloidal particles of different

morphologies, including spheres, of two drugs, loratadine and danazol, was described. In

principle these particles were obtained by precipitation when nonsolvents (water or aqueous

surfactant solutions) were added to ethanol solutions of the drug. In addition, procedures

were developed that made it possible to use the drug particles thus obtained as cores to be

then coated with either silica or aluminum (hydrous) oxide layers. The presence of these

inorganic shells was confirmed by electron microscopy, energy dispersive spectroscopy,

and electrophoresis.

Jayadev Patil et al.,18 In this work researchers had aimed to formulate and design orally

disintegrating tablets containing antihistamines like Loratadine using different

pharmaceutical compositions with simple manufacturing procedures to enhance patient

compliance. Loratadine was formulated into orally disintegrating tablets by direct

compression method using suitable excipients like Maltodextrin, Mannitol, Micro

crystalline cellulose, combination of Mannitol with Starch, Croscarmellose sodium, Citric

acid, Sodium bicarbonate along with Mint flavor, which were evaluated by using simple

analytical techniques. The taste of the formulation was enhanced using artificial sweetener

Aspartame and Mint flavour. The tablets were evaluated for weight variation, hardness,

friability, drug content, wetting time and disintegration time along with in-vitro dissolution.

It was observed that the direct compression process using commercial grades of excipients

like combination of Mannitol with Starch and Micro crystalline cellulose as directly

compressible diluents along with super disintegrants like Croscarmellose Sodium was found

to be more promising to prepare orally disintegrating tablets.

Abdul Jaleel et al.,22 in their study they have aimed on the fast dispersible tablets of

loratadine. The research was to enhance the dissolution of orally disintegrated tablets of

loratadine. Orodispersible tablets of loratadine were prepared using different types and

concentrations of superdisintegrants (Ac-Di-Sol, sodium starch glycolate, and crospovidone

(CP) (at different particle size)) using direct compression method. The drug is poorly water

soluble therefore to enhance the solubility and release of drug, solid dispersion of drug with

PVP K30 was prepared by solvent evaporation method. The formulas were evaluated for

flow properties, wetting time, hardness, friability, content uniformity, in vivo disintegration

time (DT), release profiles, and buccal absorption tests. All formulations showed

satisfactory mechanical strength and friability. The results revealed that the tablets

containing CP as a superdisintegrant have good dissolution profile with shortest DT. The

optimized formula F9 is prepared using solid dispersion of loratadine with PVPK30 at ratio

1:3 and 15% CP with lower particle size as a superdisintegrant and by direct compression

method which shows the shortest DT and good dissolution profile with acceptable stability.

It can be concluded that the orodispersible tablets of loratadine with better pharmaceutical

properties than conventional tablets could be obtained using formula F9.

Abul Kalam Lutful Kabir et al.,16 formulated and evaluated mouth dissolving tablet of

loratadine using a special preparation technology (pharmaburst Technology) with a super

disintegrating agent (Croscarmellose sodium). Tablets were prepared by direct compression

technique. The granules were evaluated for angle of repose, bulk density, tapped density,

bulkiness, compressibility index and hausners ratio. The tablets were evaluated for

hardness, thickness, uniformity of weight, friability, wetting time, water absorption ratio,

disintegration time and drug content. In vitro release studies were performed using USP-II

(paddle method) in 900ml of pH 1.2 at 50rpm. The physical properties of the prepared

tablets did not show any significant variations and were found to have good physical

integrity. Tablets prepared with pharmaburst B2 and Croscarmellose sodium showed a

lesser disintegration time and wetting time of 27±0.10 and 38±0.13 seconds respectively.

The best formulations were subjected to stability studies at 40ºC/75% RH for 60 days.

Kei-ichi Koizumi et al.,38 have used a sublimation technique for manufacturing of fast

disintegrating tablets. Compressed tablets of a water-soluble material, prepared using

mannitol, did not rapidly dissolve in water since it is difficult for water to penetrate into the

tablets due to their low porosity. To increase the porosity of the tablets which are prepared

by direct compression using mannitol, have researchers developed a novel method whereby

camphor, a subliming material, is removed by sublimation from compressed tablets

prepared using a mixture of mannitol and camphor. A high porosity was achieved due to the

formation of many pores where camphor particles previously existed in the compressed

mannitol tablets prior to sublimation of the camphor. These compressed tablets which have

high porosity (approximately 30%) rapidly dissolved within 15 s in saliva in the mouth.

They developed a direct compression method for the preparation, using mannitol and

camphor, of a meclizine (antidinic agent) tablet with high porosity which dissolves rapidly

in saliva.

ZHANG Yi-Fan et al.,22 aimed to investigate the pharmacokinetics of loratadine (LOR)

and its active metabolite descarboethoxyloratadine (DCL) in healthy Chinese subjects. The

method consisted of twenty healthy Chinese male subjects received a single oral dose of

LOR 20 mg. A sensitive liquid chromatography-tandem mass spectrometry method

(LC/MS/MS) was used for the determination of LOR and DCL in plasma. The results

showed that mean maximum concentration (Cmax) was found (17±14) µg/L for LOR at 1.2

h and (16±9) µg/L for DCL at 1.5 h. Mean area under the plasma concentration-time curve

from zero to infinity (AUC0--) was (47±49) µg.h.L-1 for LOR and (181±122) µg.h.L-1 for

DCL, respectively. The apparent elimination half-life (T1/2) of LOR was (6±4) h, and that

of DCL was (13.4±2.6) h. The ratios of AUCDCL/ AUCLOR ranged from 0.36 to 54.5. The

final conclusion made was that LOR was rapidly absorbed and transformed to DCL. AUC

of the parent drug was extremely variable, while AUC of the active metabolite DCL was

moderately variable after an oral dose of LOR to Chinese subjects.

Shashi Kiran Mishra et al.,13 formulated a controlled release system of loratadine to

increase the residence time in stomach and to modulate the release behaviour of the drug.

Oil entrapped floating microbeads prepared by the emulsion gelation method were

optimized by 23 factorial design and a polymer ratio of 2.5:1.5 (pectin/sodium alginate) by

mass, 15% (m/V) of oil (mineral oil or castor oil) and 0.45 mol L–1 calcium chloride

solution as the optimized processing conditions for the desired buoyancy and physical

stability. In vitro drug release in the fed state conditions demonstrated sustained release of

loratadine for 8 h, which best fitted the Peppas model with n < 0.45. The ethyl cellulose

coating on microbeads optimized by 22 factorial design resulted in a controlled release

formulation of loratadine that provided zero-order release for 8 h.

M. Zahirul I. KHAN et al.,21 in this research paper Loratadine was studied both in vitro

and in vivo (in healthy humans) to classify it according to the Biopharmaceutics

Classification System (BCS) in order to gain more understanding of the reasons for its

highly variable nature with respect to plasma time profiles, and to determine the most

appropriate dissolution test conditions for in vitro assessment of the release profile of the

drug from solid dose forms. Based on the solubility of loratadine determined under various

pH conditions and its permeability through Caco-2 monolayers, loratadine was classified as

a Class II drug. Plasma profiles were predicted by convolution analysis using dissolution

profiles obtained under various pH and hydrodynamic conditions as the input function and

plasma time data obtained from a syrup formulation as the weighting function. The

predicted profiles based on dissolution studies done at gastric pH values were in reasonable

agreement with the mean bio-data suggesting dissolution testing should be done at gastric

pH values. However, the bio-data were highly variable and it is suggested this may be due,

at least in part, to high individual gastric pH variability and dissolution occurring in the

intestine on some occasions, and therefore, dissolution testing should also be done in

simulated intestinal fluid.

Lars Pedersen et al.,20 examined the risk of hypospadias after exposure to loratadine and

other antihistamines during pregnancy, we conducted a population-based case-control study

in four Danish counties, which account for 30% of the Danish population (~1.6 M). We

obtained data on maternal use of antihistamines from prescription databases, and data on

birth outcomes from the Danish Medical Birth Registry (MBR) and the Hospital Discharge

Registry (HDR). A total of 65,383 male births with a full prescription history of the mother

in the study period from 1989-2002 were available for analysis. Within this cohort, we

identified cases with a diagnosis of hypospadias, and 10 selected controls per case without

such a diagnosis (matched on birth month, gender and year of birth). We identified 227

cases of hypospadias recorded in the HDR within six months postpartum and 2270 controls.

One case (0.4%) and eight (0.4%) controls were exposed to loratadine in the first trimester

and up to 30 days before the time of conception. The adjusted odds ratio (OR) for

hypospadias among users of loratadine relative to non-users was 1.4 (95% CI: 0.2-11.2) and

the corresponding OR for other antihistamines was 1.9 (95% CI: 0.7-5.7). In this study,

maternal exposure to loratadine did not appear to be associated with an increased risk of

hypospadias when compared with other antihistamines, although it should be noted that the

statistical precision of the risk estimates might be limited.

Dr. C.S.R. Lakshmi et al.,37 compared the effect of subliming agents on the oral

dispersible property of cinnarizine tablets. The fundamental principle used in the

development of the oral dispersible tablets by sublimation technique is to maximize pore

structure of the tablets. Compressed tablets prepared using a water soluble material like

mannitol, does not rapidly disperse in water since it is difficult for water to penetrate into

the tablets due to their low porosity. To increase the porosity of the tablets which are

prepared by direct compression using mannitol, subliming agents such as camphor,

menthol, ammonium bicarbonate or thymol are to be used. A high porosity was achieved

due to the formation of many pores where camphor, menthol, ammonium bicarbonate and

thymol particles previously existed in the compressed mannitol tablets prior to sublimation

of these subliming materials. These compressed tablets which have high porosity

(approximately 30%) rapidly dissolved within 25 s in the mouth. We developed a direct

compression method for the formulation of cinnarizine (an anti emetic drug) tablets with

high porosity which dissolves rapidly using mannitol as diluent and camphor, menthol,

ammonium bicarbonate or thymol as subliming agents.

Capokova Z. et al.,17 dealed with the formulation of the antihistaminic into Loratidine into

hydrogels. The polymer carbopol 980 in concentrations 0.5, 0.8 and 1 % was evaluated. The

aim of the study was to develop an optimal concentration of carbopol 980 for the

formulation of hydrogels. The choice of optimal concentration is based on the rheological

properties of hydrogel as well as the pharmaceutical availability of loratadine from

hydrogels. Obtained results imply that, from the viewpoint of a topical application, the

optimal concentration of carbopol 980 for the formulation of hydrogels with loratadine is

0.5 % w/v.

Behzad Sharif Makhmal Zadeh et al.,24 aimed their study to formulate a SEDDS

containing a lipophilic drug, loratadine, and to explore the potential of carriers for such

system. For opportunity to perfect formulation, full factorial design with three variables;

surfactant/oil, surfactant/co-surfactant proportion and percentage of drug in two levels were

used. The effects of variables on formulation characters; emulsifying efficiency, particle

size, drug release and rat intestine permeability were evaluated. The results showed liquid

paraffin and labrafil as oil with span 20 as surfactant and capriol as co-surfactant prepared

stable emulsions with refractive index higher than acidic medium and water. The particle

sizes of formulations were influenced by type of oil, in the manner that liquid paraffin

induced lower particle size in the range of 0.28- 1.8 micron. The percentage of drug release

after 6 hrs for labrafil and liquid paraffin were 30.87-54.26% and 31.99-61.34 respectively.

Formulations prepared with liquid paraffin and labrafil demonstrated drug permeability

through rat intestine 2.72 and 2.25 folds compared to control. Comparison between drug

release and in vitro permeability indicated that drug release from formulation after mixing

with acidic condition is rate limiting for gastric absorption. In conclusion SEDDS prepared

with liquid paraffin provided perfect solubility in acidic condition and increased intestinal

permeability.

Savan R. Vachhani et al.,15 focused on the development of hydrodynamically balanced

delivery system of loratadine as a single unit floating capsules. Sustained release floating

capsules for loratadine were fabricated using drug:polymer ratio of 1:4. The hydrocolloids

were used in different proportions using 32 full factorial design and formulations were

prepared. These formulations were optimized on the basis of buoyancy, matrix integrity,

duration of floating and in vitro drug release. All the nine formulations showed good

buoyancy and matrix integrity. The duration of floating was more than 12 h for all

formulations. In vitro drug release study of these formulations indicated controlled release

of loratadine and about 90 percent drug was released at the end of 12 h.

V. Felix Joe et al.,14 aimed to develop extended release tablets of pseudophedrine

hydrochloride and loratadine using hydroxy propyl methyl cellulose and sodium

carboxymethylcellulose in different proportions a matrix material in core tablet and

loratadine is used as immediate release for this a film coating formula was developed, so as

to provide immediate release from the zone of coating. The results of the dissolution study

indicated the formulations FC – VI and FC – VII showed maximum drug release up to 12

hr, the release of the drug was found to be dependent on the relative proportions of

hydroxypropylmethylcellulose and sodiumcarboxymethylcellulose used in core tablet.

Mathematical treatment of the in vitro drug release data suggests that, all the formulations

best fitted into first order release kinetics. Drug release from the matrix occurred by

combination of two mechanisms, diffusion of drug from tablet matrix and erosion of tablet

surface.

Georgeta Pavalache et al.,36 developed a novel technique for the loratadine determination

from tablets by UV. At present, loratadine is studied by spectrophotometry, high-

performance liquid chromatography and electrospray mass spectrometry. This paper

describes the development of a method for determination of loratadine by ultraviolet

spectrophotometry: loratadine methanolic solution and complex ion tetraiodomercuriat

[HgI4]2- form a compound in the presence of hydrochloric acid. The 380nm maximum

absorbance of the compound is proportional to its concentration in loratadine. The

experiment establishes the appropriate working conditions (reaction environment, the

optimal amount of reagent, the reaction time, etc.). The advantages of this sensitive method

make it an efficient way to analyze loratadine from different types of samples.

6.3 OBJECTIVE OF STUDY

Loratadine is sparingly soluble in water but freely soluble in the pH of 1.2 to 2.0. The Pka

of loratadine is 4.3. It is extensively absorbed from the gastric pH. A reduction in gastric

transit time may cause the drug to move into the alkaline pH of the intestine. This may

cause a reduction in the absorption of the drug. Hence a fast disintegrating tablet may help

to overcome the above mentioned problems and can lead to increase in the bioavailability.

So the present study is planned with the following objectives:

To prepare Fast Disintegrating tablets of Loratadine by sublimation method with the

incorporation of superdisintegrants.

To carry out compatibility study between drug and carriers or complex.

To study in vitro drug release profile.

To study the effect of sublimation and superdisintegrants on dissolution

characteristics.

To carry out preformulation studies.

To carry out Stability studies of sublimed tablets as per the ICH guidelines.

7 MATERIALS AND METHODS

7.1 Drug

Superdisintegrants and other additives

Method

Loratadine

Mannitol, crospovidone, Menthol, Camphor / any other suitable material

Sublimation technique

SOURCE OF DATA

The data was collected from the following resources:

1. College Library

2. RGUHS digital library (Helinet)

3. Science Direct, Wikipedia, Pubmed, Free and Commercial websites providing

information online etc

4. Various Research Journals available online

a. International Journal of Pharmaceutics

b. Indian Journal of Pharmaceutical Sciences

c. International Journal of Pharmaceutical Sciences Review and Research

d. International Journal of Pharma Sciences

e. International Journal of Pharma and Bio Sciences

f. International Journal of Pharm Tech Research

g. International Journal of Medical Sciences

h. Stamford Journal of Pharmaceutical Sciences

7.2

i. Journal of Pharmacy Research

j. Journal of Chemical and Pharmaceutical Research

k. Journal of Colloid and Interface Science

l. Research Journal of Pharmaceutical, Biological and Chemical Sciences

m. Tropical Journal of Pharmaceutical Research

n. Recent Patents on Drug Delivery & Formulation

o. Acta Pharmacol

p. Biological and Pharmaceutical Bulletin

q. Acta Pharm

r. Scientia Pharmaceutica

s. Drug Invention Today

t. Scholar Research Library

METHOD OF COLLECTION OF DATA

Sr No. Test 1. Preformulation Studies

2. Physical Characterizations

Particle size and size distribution (SEM)

Surface morphology (TEM / SEM)

Conformation of absence of chemical interaction between drug and polymer (FTIR)

Confirm compatibility between drug and excipients (DSC)

Angle of Repose

Bulk density (BD)

Tapped density (TD)

Carr’s Index

Hausner’s Ratio

3. Thickness

4. Crushing Strength

5. Friability

6. Drug Content Uniformity

7. Weight Variation

8. Wetting Time

9. In-vitro Disintegration Test

10. In-vitro Dissolution Test

11. Test for Dispersion

12. Stability studies as per ICH Guidelines

7.3 Does the Study Require any investigations or invention to be conducted on

patients or other human or animals? If so Please mention briefly.

NA

7.4 Has ethical clearance been obtained from your institution case 7.3?

NA

8. REFERENCES

1. Bhupendra G Prajapati and Nayan Ratnaka; A Review on Recent patents on Fast

Dissolving Drug Delivery System, “International Journal of Pharm Tech Research”,

Vol.1, No.3, pp 790-798 , July-Sept 2009

2. Sandeep Divate et al., Fast Disintegrating Tablets – An Emerging Trend, “International

Journal of Pharmaceutical Sciences Review and Research”, Volume 6, Issue 2, January

– February 2011; Article-005

3. Lokesha Puttalingaiah et al., Fast disintegrating tablets: An overview of formulation,

technology and evaluation “Research Journal of Pharmaceutical, Biological and

Chemical Sciences”, April – June 2011 RJPBCS Volume 2 Issue 2 Page No. 589

4. Honey Goel et al., Orally Disintegrating Systems: Innovations in Formulation and

Technology, “Recent Patents on Drug Delivery & Formulation”, 2008, 2, 258-274

5. Rakesh Pahwa et al., Orally Disintegrating Tablets - Friendly to Pediatrics and

Geriatrics, “Scholar Research Library, Archives of Applied Science Research”, 2010, 2

(2): 35-48

6. Sudhir Bharawaj et al., Orally Disintegrating Tablets: A Review, “Drug Invention

Today”, 2010,2(1),81-88

7. Jaysukh J Hirani et al., Orally Disintegrating Tablets: A Review, “Tropical Journal of

Pharmaceutical Research”, April 2009; 8 (2): 161-172

8. Mukesh P. Ratnaparkhi et al., Review On: Fast Dissolving Tablet, “Journal of

Pharmacy Research”, Vol.2.Issue 1. January 2009

9. Dali Shukla et al., Mouth Dissolving Tablets II: An Overview of Evaluation

Techniques, “Sci Pharm.”, 2009; 77: 327–341

10. P.S Mohanachandran, Superdisintegrants: An Overview, “International Journal of

Pharmaceutical Sciences Review and Research”, Volume 6, Issue 1, January –

February 2011; Article-022

11. E. M. Samy et al., Formulation and Development of Loratadine Floating Tablets: In-

vitro and In-vivo Evaluation,

12. K Kathiresan et al., Formulation and evaluation of loratadine chewable tablets,

“Research Journal of Pharmaceutical, Biological and Chemical Sciences”, October –

December 2010 RJPBCS 1(4) Page No. 763

13. Shashi Kiran Mishra et al., Formulation and evaluation of oil entrapped gastroretentive

floating gel beads of loratadine, “Acta Pharm.”, 58 (2008) 187–197

14. V. Felix Joe et al., Formulation and evaluation of Pseudoephedrine hydrochloride and

Loratadine extended release tablet, “J. Ph. Res.”, 2011,4 (2),507-508

15. Savan R. Vachhani et al., Formulation and in-vitro evaluation of floating capsules of

Loratadine, “J. Chem. Pharm. Res.”, 2010, 2(2): 57-64

16. Abul Kalam Lutful Kabir et al., Formulation Development and Evaluation of Mouth

Dissolving Tablets of Loratadine, “Stamford Journal of Pharmaceutical Sciences”,

2(2): 59-65 2009

17. Capkova et al., Formulation of Loratadine into Hydrogels, “Acta Facultatis

Pharmaceuticae Unerversitatis Comenianae Tomous” L II 2005

18. Jayadev Patil et al., Formulation, Design And Evaluation Of Orally Disintegrating

Tablets Of Loratadine Using Direct Compression Process, “International Journal of

Pharma and Bio Sciences”, Vol 2 / Issue 2 / Apr-Jun 2011

19. M. Zahirul I. KHAN et al., Classification of Loratadine Based on the Biopharmaceutics

Drug Classification Concept and Possible in Vitro–in Vivo Correlation, “Biol. Pharm.

Bull.”, Vol. 27, No. 10, 1630—1635 (2004)

20. Lars Pedersen et al., Maternal use of Loratadine during pregnancy and risk of

hypospadias in offspring, “International Journal of Medical Sciences”, 2006 3(1):21-25

21. ZHANG Yi-Fan et al., Pharmacokinetics of loratadine and its active metabolite

descarboethoxyloratadine in healthy Chinese subjects, “Acta Pharmacol Sin”, 2003 Jul;

24 (7): 715-718

22. Abdul Jaleel, Omar W, Preparation and Characterization of Orally Disintegrating

Loratadine Tablets from PVP Solid Dispersions, “INT.J.PH.SCI.”, SEP - DEC,

2010;2(3):759-770

23. Sreˇco D. Škapin et al., Preparation and coating of finely dispersed drugs 4. Loratadine

and danazol, “Journal of Colloid and Interface Science”, 272 (2004) 90–98

24. Behzad Sharif Makhmal Zadeh et al., Preparation and evaluation of the self emulsifying

drug delivery system containing loratadine, “International Journal of Advances in

Pharmaceutical Sciences”, 1 (2010) 239-248

25. US PATENT, Stable Loratidine Spill Resistant Formulation, Patent No. US 7,758,877

B2, Date of Patent Jul 20 2010

26. I Singhvi, Visible Spectrometric Methods for the Estimation of Loratadine From

Tablets, “Indian Journal of Pharmaceutical Sciences”, Vol. 65, Issue 3, 2003, pg. no.

291-293.

27. Shan-Yang Lin et al., Curve-fitting FTIR studies of loratadine/hydroxypropyl-

cyclodextrin inclusion complex induced by co-grinding process,

doi:10.1016/j.jpba.2010.06.010.

28. Excipient for fast-disintegrating oral dosage forms Direct compressible formula,

Ludiflash®, Technical Information January 2009, Supersedes issue dated April 2008

29. Wayne Camarco et al., Selecting Superdisintegrants for Orally Disintegrating Tablet

Formulations, Reprinted from “Pharmaceutical Technology Supplement”, October 2006

30. J.A. Westerhuis et al., Optimisation of the composition and production of

mannitol/microcrystalline cellulose tablets, “Int. J. Ph.”, 143 (1996) 151-162

31. Hong Wen et al., Oral Controlled Release Formulation Design And Drug Delivery -

Theory to Practice, 2010, John Wiley & Sons, Inc, Pg no. 155 – 167

32. Physician’s Drug Reference, Thomas Healthcare, 62nd edition, 2008, pg. no. 2939

33. Leon Lachman, H.A.Lieberman; The Theory and Practice of Industrial Pharmacy; 3rd

edition; Varghese Publishing House.

34. USP29–NF24, Page 1273, Pharmacopeial Forum : Volume No. 30(6) Page 2011

35. Laurence L. Brunton et al., Goodman and Gilman’s – The Pharmacological basis of

Therapeutics , 11th Edition, Mc Graw Hill, 2006, Pg. no. 629-651

36. Georgeta Pavalache et al., Validation of UV molecular absorption spectrometric method

for loratadine determination, “Ovidius University Annals of Chemistry”, Volume 21,

Number 2, pp. 157-162, 2010

37. Dr. C.S.R. Lakshmi et al., Formulation And Evaluation Of Oral Dispersible Tablets Of

Cinnarizine Using Sublimation Technique, “International Journal of Pharmaceutical

Sciences Review and Research”, Volume 6, Issue 2, January – February 2011; art - 032

38. Kei-ichi Koizumi et al., New method of preparing high-porosity rapidly saliva soluble

compressed tablets using mannitol with camphor, a subliming material, “J. Ph. Res.”

s152 (1997) 127 131

9 Signature of Candidate

10 Remarks of the Guide

The above information is true to the best

of my knowledge and the work will be

done under my guidance.

11. Name and Designation of

11.1 Institutional Guide

Mrs. Sujata P. MuchalambeAsst. Professor

Department of Pharmaceutics R R College of Pharmacy

Bangalore – 560 090

11.2 Signature

11.3 Co – Guide, if any -

11.4 Signature -

11.5 Head of Department

Dr. L. PRABAKARANProfessor& HOD

Dept. of Pharmaceutics,RR College of Pharmacy,

Bangalore-560 090

11.6 Signature

12. 12.1 Remarks of the Principal The above mentioned is correct and I recommend the same for approval.

12.2 Signature Dr. B. GOPALAKRISHNAPrincipal

R.R College of Pharmacy,

Bangalore-560 090