“FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETS OF LORATADINE HYDROCHLORIDE”

BY

SHILPA SHREE. S

DEPARTMENT OF PHARMACEUTICS

DISSERTATION PROTOCOL

SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BENGALURU-560041

KARNATAKA

UNDER THE GUIDANCE OF

VASEEHA BANU T.S. M.Pharm (Ph.D)

ASSISTANT PROFESSOR

DEPARTMENT OF PHARMACEUTICS

M.M.U COLLEGE OF PHARMACY

RAMANAGARAM-562159

KARNATAKA

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BENGALURU KARNATAKA

AnneXUre II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1 / NAME OF THE CANDIDATE AND
ADDRESS (IN BLOCK LETTERS) / SHILPA SHREE.S
SRINIVASA NELAYA
BEHIND JAI BHARATH PETROL BUNK(OLD)
B.M ROAD, VIDYANGAR, RAMANAGARA-562159
2 / NAME OF THE INSTITUTION / MMU COLLEGE OF PHARMACY
K.K.DODDI. RAMANAGARA-562159 RAMANAGARA (DIST), KARNATAKA
3 / COURSE OF THE STUDY AND SUBJECT /

MASTER OF PHARMACY IN PHARMACEUTICS

4 / DATE OF ADMISSION TO THE COURSE / 29-06-2013
5 / TITLE OF THE TOPIC / FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETS OF LORATADINE HYDROCHLORIDE.ESIS
6 / BRIEF RESUME OF THE INTENEDED 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
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 / VASEEHA BANU T.S.
ASST. PROFESSOR,
DEPARTMENT OF PHARMACEUTICS,
M.M.U COLLEGE OF PHARMACY,
K.K DODDI, RAMADEVERA BETTA ROAD, RAMANAGARA-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, RAMANAGARA-562159,
KARNATAKA
12 / 12.1 Remarks of the chairman and principal
12.2 Signature

6.0 BRIEF RESUME OF THE INTENDED WORK

ENCLOSURE-I

6.1 NEED FOR THE STUDY

Oral route is the most preferred route of administration of various drugs. Tablet is the most popular oral dosage forms existing today because of convenience of self-administration, compactness and easy manufacturing. However, patients especially elderly find difficulty in swallowing tablets and capsules thus don’t comply with prescription1. Difficulties in swallowing also occurs when water is not available, in diarrhoea, coughing, during common cold, allergic condition and bronchial infection.2 Approximately one-third of population has found difficulties in swallowing tablets and capsules, resulting in poor compliance and ineffective therapy. For these reasons, tablets that can rapidly dissolve or disintegrate in the oral cavity have attracted a great deal of attention3. Fast dissolving tablets are solid dosage form containing medicinal substance or active ingredient which disintegrate rapidly usually with a matter of seconds when placed upon the tongue.4

Loratadine is a second-generation, antihistamines drug (H1-receptor antagonist), which works by blocking the action of Histamine. It lacks the CNS depresent effect and mainly used to temporarily relieve the symptoms of hay fever (allergy to pollen, dust, or other substances in the air) and other allergies. These symptoms include sneezing, runny nose, and itchy eyes, nose, or throat. Loratadine is also used to treat itching and redness caused by hives5 6.

Loratadine absorbed rapidly when given orally and undergoes extensive first-pass hepatic metabolism it is metabolized by isoenzymes of the cytochrome P450 system, including CYP3A4, CYP2D6. Loratadine is almost totally (97–99%) bound to plasma protein and half-life is on average 8 hr 5 6.

It is well known that faster dissolution of tablets results in fast absorption and onset of action. Allergic condition requires the immediate medication and immediate relief. Some drugs are absorbed from mouth, pharynx and esophagus as the saliva passes down the stomach. In such cases the bioavailability is greater than those observed for conventional dosage form7.

In the present study, we propose to develop fast dissolving tablets of Loratadine hydrochloride for rapid onset of action in allergic condition and the easiest way to administer a drug for pediatric and geriatric patients.

ENCLOSURE-II

6.2 REVIEW OF LITERATURE

  1. Patro Chandrashekar, patro sreenivas S: Fast dissolving tablets of cetirizine hydrochloride were prepared using different superdisintegrants by direct compression method. Fast dissolving tablets were evaluated for physicochemical properties and in vitro dissolution. The drug release from fast dissolving tablets increased with increasing concentration of superdisintegrants. The release of cetirizine hydrochloride from fast dissolving tablets was found to follow non-fickian diffusion kinetics8.
  2. Ghorwade vijaykumar, Patil Ajaykumar, Patil sudheer, Ikkurhi krishnakanth, Inuganti sujan Krishna, porandla Vishal: In this study mouth dissolving tablets of montelukast were prepared toachieve a better dissolution rate and further improving the bioavialabilty of the drug. Mouth dissolving tablets prepared by direct compression and using super disintegrants like Polyplasdone XL 10, Croscarmellos sodium and Explotab in different concentration and evaluated for the pre-compression parameters. Among all, the formulation containing 5%w/w superdisintegrant Polyplasdone XL 10 was considered to be best formulation, which release up to 99.26% in 12 minutes9.
  3. Rasheed Haru Shaik, Arief Mulla: Mouth dissolving tablets of salbutamol were prepared using different superdisintegrants by sublimation method. Different concentrations (2%, 4% and 6%) of superdisintegrants such as Ac-Di-Sol, sodium starch glycolate, Kollidon-CL were used respectively. Camphor was used as a sublimation agent. The result revealed that the dissolution rate and disintegration time can be improved by using camphor as the sublimating agent and with the addition of superdisintegrants10.
  4. .Kulkarni U, Raghavendra NG, Hariprasanna RC, Rabbani G, Patil BS: Fast dissolving tablets of Aceclofenac were prepared by employing sublimation method to study the effect of different subliming agents and fillers. Drug compatibility with excipients was checked by FT-IR studies. The results revealed that quantity of camphor, menthol, urea and type of filler significantly affect the response variablets11.
  5. Chaudhari PD, Chaudhri SP, Lanke SD and Patel: In this study attempt has been made to prepare fast dissolving tablets of Levocetrizine dihydrochloride in the oral cavity with enhanced dissolution rate. The tablets were prepared with five superdisintegrants eg; Sodium starch glycolate, Crospovidone, Croscarmellose, L-Hydroxy propyl cellulose, pregelatinised starch. It was concluded that fast disintegrating tablets of Levocetrizine can be successfully prepared by selecting suitable superdisintegrants in order to improve disintegrants/dissolution of the drug in oral cavity12.
  6. Chhandira RM, Venkataeswarlu BS, Kumudhavalli MV, Bhwmik D, Jayakar B: In this investigation, mouth dissolving tablets of Etoricoxib were formulated by direct compression method using various superdisintegrants such as kollidone, AC-Di-sol, primogel, L-Hydroxy propy cellulose, L-Hydroxypropyl methyl cellulose in different concentration like 4% and 8%. The result revealed that the formulation containing (8% L-Hydroxy propyl cellulose) showed minimum disintegration time, wetting time as compared to other formulation. Dissolution studies concluded that 97% of the drug was released at the end of 20 minutes and disintegration time was increased in the manner of L-Hydroxy propyl cellulose <Kollidone<AC-Di-sol<Primogel<L-Hydroxypropyl methyl cellulose13.
  7. Kalia A, Khurana S, Bedi N: In this study, the mouth dissolving tablets of Oxcarbazepine were prepared using two different technologies, direct compression method and solid dispersion technology. Tablets produced be direct compression method contain crospovidone as a superdisintegrant and aspartame as a sweetener. Solid dispersions of oxcarbazepine with polyvinylpyrrolidone K-30 and plyethylene glycol 6000 in different weight ratios were prepared with a view to increase its water solubility. The results compared for both the technologies showed that the oxcarbazepine tablets prepared using solid dispersion technology was found to have good technological properties and satisfying reproducible drug dissolution profiles14.
  8. Patil S. Basawaraj, Rao Raghavendra NG: Fast dissolving tablets of granisetron hydrochloride were designed be direct compression method using disintegrant blend with a view to enhance patient compliance. A combination of super- disintegrants ie. Sodium starch glycolate-crospovidone, sodium starch glycolate croscarmellose sodium and sodium starch glycolate-L-Hydroxy propyl cellulose were used along with directly compressible mannitol to enhance mouth feel. The result declears that the formulation prepared by direct compression method using 4.0% w/w sodium starch glycolate and 2.0% w/w of crospovidone was found to be promising formulation based on the in vitro drug release characteristics compared to control tablet formlation15.
  9. K Kathiresan et al., Formulation and evaluation of Loratadine chewable tablets by using microcrystalline cellulose, guar gum and povidone as polymers and maize starch as binding agent. The result revealed that the formulation containing Microcrystalline 70% and guar gum 30% and starch paste showed better physical character of chewable tablet and better dissolution profile, so it was concluded that Loratadine chewable tablet can be prepared to improve patient compliance16.
  10. Bhalerao AV et al., In this study, the mouth disintegrating tablet of Clonazepam were prepared using different combinations of superdisintegrants such as Crosscarmellose sodium, sodium starch glycolate, crospovidone. Directly compressible monnitol, and aspartame were used to enhance the mouth feel and taste. Lactose was used as diluents. The tablets were prepared by direct compression technique on rotary tablet machine. The tablets were evaluated for hardness, friability, weight variation, wetting time, dispersion time and uniformity of content. Optimized formulations were evaluated by in vitro dissolution test. The result revealed that amongst all formutations, formulation F10 prepared by drug PVP K 30 (1:4) ratio by solvent evaporation and combination of 5%w/w crosscarmellose sodium and 5% w/w of sodium starch glycolate showed least dispersion time of 8s and faster dissolution17.
  1. ENCLOSURE-III

6.3 OBJECTIVES OF THE STUDY

  1. To select suitable super disintegrant for the preparation of Fast dissolving tablets.
  2. To formulate Loratadine hydrochloride Fast dissolving tablet.
  3. To evaluate physicochemical properties for the prepared formulation.
  4. To carry out in-vitro release study of tablets.

MATERIALS AND METHODS:

Materials:

Drug: Loratadine hydrochloride

Super disintegrant: Crospovidone, Sodium starch Glycolate, Kollidone, croscarmellose sodium etc.

Methods:

Loratadine hydrochloride fast dissolving tablets prepared by following method.

  • Direct compression.

ENCLOSURE-IV

7.1 SOURCE OF DATA

The preliminary data required for the experimental study is obtained from-

  1. Scientific abstracts.
  2. Journals:
  3. Indo Global journal of pharmaceutical science.
  4. International Research journal of Pharmacy.
  5. International research journal of pharmacy.
  6. Bangladesh Pharmaceutical Journal.
  7. Indian journal of pharmaceutical science.
  8. Pubmed-wikipedia.
  9. MedPlus.
  10. Drugs.com
  11. Internet sources and Relevant Books.
  12. Relevent articles.
  13. Research articles from experts.
  14. Library-MMU college of Pharmacy.
  15. Laboratory based studies.

ENCLOSURE-IV

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 formulations 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
  1. Preparation of tablets:
  2. Direct compression method.
  3. Evaluation parameters: weight variation, hardness, friability, disintegration, wetting time & water absorption ratio, content uniformity, in-vitro dissolution study etc. (as per Indian pharmacopoeia).

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. Seager H. Fast dissolving dosage form. J. Pharma. Pharmacol.1998;50(4): 375-382.
  1. Habib W., Khankari R., Hontz J. Fast dissolving drug delivery systems, critical review in therapeutics. Drug carrier systems. 2000;17(1):61-72.
  1. Siddqui M. N., Garg G., Kumar P. Preparation, characterization and evaluation of fast dissolving tablets. Int J. of Pharm. & pharmaceutical sci. Review and Research. 2010; 4 (2): 87-90.
  1. Allen L. V., and Wang B. Particulate support matrix for making a rapidly dissolving tablet, US Patent 5595761. Int. J. of Pharm and pharmaceutical science. 1997;4 (2): 15.
  1. Loratadine- Wikipedia; Drug properties of Loratadine hydrochloride. Drugs.com
  1. Loratadine- Wikipedia; medplus.
  1. Pebley W. S., Jager N. E., Thompson S. J. Rapidly disintegrating tablets, US Patent no.5,298,261 ,1994. Int.J. Pharm Sciences Review and Research.
  1. Patro C., Patro S. S. Formulation and evaluation of fast dissolving tablets of Cetrizine HCL. Scholars Research Library, 2011; 3(4):63-70.
  1. Ghorwade V., Patil A. K., Patil S. Formulaiton and evalution of fast dissolving tablet of Montelukast Sodium. Research J. of Pharm Sci. 2011;.2(3):880-885.
  1. Tasheed S. H., Arief M., Gajavali S. R. Design of fast dissolving tablets of salbutamol. Int.J. of Pharma Science, 2011; 2 (2) : 155-159.
  1. Kulkarni U., Raghavendra N. G., Hariprasanna R. C., Rabbani G., Patil B. S. Formulation development of aceclofenac fast dissolving tablets; Effect of functionality of subliming agents. J App Pharm. 2011; 02(03): 179-190.
  1. Chaudhari P. D., Chaudhri S. P., Lanke S. D., Patel. Formulation and evaluation of taste masked orodispersible dosage form of levocetrizine dihyrochloride. Indian Journal of Pharm.Educ,Res, 2007; 41(4):319-328.
  1. Chhandira R. M., Ventkataeswarlu B. S., Kumudhavalli M. V., Bhwmik D, Jayakar B. Formulation and evaluation of mouth dissolving tablets of the etoricoxib. Pak. J. Pharm. Sci 2010;23(2): 178-181.
  1. Kalia A., Khurana S., Bedi N. Forumlation and evaluation of mouth dissolving tablet of oxcarbazepine. Int J. of Pharm and pharmaceutical sci. 2009;1(1): 12-23.
  1. Kumar D. N., Raju S. A., Shirsand S. B., Para M. S. Formulation design of fast dissolving tablets of granisetron. Int. J. of Res. In Ayur. and Pharm. 2010; 1(2); 468-474.
  1. Kathiresan K. et al., Formulation and evaluation of loratadine chewable tablets, “Research Journal of Pharmaceutical, Biological and Chemical Sciences”, 2010;1(4);763-766
  1. Bhalerao A. V. et al., Development and Evaluation of Clonazepam Fast Disintigrating Tablets Using Superdisintigrates and Solid Dispersion Technique, “Research J. Pharm. And 2009;Tech.2(2): 375-377.

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