Formulation and Evaluation Of

FORMULATION AND EVALUATION OFANTI HISTAMINESUPPOSITORIES

SYNOPSIS FOR

M.PHARM DISSERTATION

SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

KARNATAKA

PRAVEEN KUMAR SINGH

I M.PHARM

UNDER THE GUIDENCE OF

MR. RAJARAJAN.S

ASSISTANT PROFESSOR

DEPARTMENT OF PHARMACEUTICS

KARNATAKA COLLEGE OF PHARMACY

BENGALURU-560064 (2011-2013)

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

KARNATAKA, BANGALORE.

ANNEXURE II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1 / Name of the Candidate and Address / PRAVEEN KUMAR SINGH
Karnataka College of Pharmacy
# 33/2, Thirumenahalli
Hegde Nagar Main Road
Bengaluru-560064.
PERMANENT ADDRESS S/O. ANJANI KUMAR SINGH
Village+Post-PATOI, Dist-.BALLIA,
STATE- UTTAR PRADESH
PIN CODE-221716.
2 / Name of the Institution / KARNATAKA COLLEGE OF PHARMACY
# 33/2, Thirumenahalli
Hegde Nagar Main Road
Bengaluru-560064.
3 / Course of the Study and Subject / MASTER OF PHARMACY IN
PHARMACEUTICS
4 / Date of Admission / 20th SEPTEMBER- 2011
5 / TITLE OF THE PROJECT:-FORMULATION AND EVALUATION OFANTI HISTAMINE
SUPPOSITORIES
6
6.1
6.2 / BRIEF RESUME OF INTENDED WORK:-
NEED FOR THE STUDY:-
The rectal route of drug delivery have been recognized as an alternative to the oral route in situations such as when the patient is comatose, unable to swallow or when the drug produces nausea or vomiting. There are several therapeutic reasons why a drug should be administered rectally than orally. One of these is that, it is possible to avoid partly hepatic first pass elimination following rectal administration.
The ideal suppository would be easy to administerwith good patient compliance and remain atthe administered sites avoiding the first pass effectin the liver and the gastrointestinal tracts. It has been accepted that at least 50-70% of a drug suitable for rectal administration is absorbed via the above direct pathway. It is well recognized that drug absorption after rectal administration is in agreement to a considerable extent with the pH partition theory. In the light of this, efforts have been made in recent times to present a good number of drugs in suppository formatting for the needs of the individual patient.
Antihistamines are used to relieve or prevent the symptoms of hay fever and other types of allergy. They work by preventing the effects of a substance called histamine, which is produced by the body. Histamine can cause itching, sneezing, runny nose, and watery eyes. Also, in some persons histamine can close up the bronchial tubes (air passages of the lungs) and make breathing difficult. Some of the antihistamines are also used to prevent motion sickness, nausea, vomiting, and dizziness. Antihistamines are available as conventional solid and liquid oral dosage forms, Suppository as well.
In the present study, we, therefore, focused to prepare and evaluate suppositories of Antihistamine by employing suitable solid fats. Antihistamines will be chosen as a model drug. The further study includes physicochemical properties of the suppositoriessuch as viscosity, melting behaviour and in vitrodrug release profile were evaluated and stability studies will be conducted as per the ICH guidelines.
REVIEW OF LITERATURE:

The release of acetaminophen (AAP), a model drug, from suppositories was delayed by HB750, PS500 or beeswax, and an excellent correlation was observed between the apparent viscosity of these mixed bases and Higuchi’s rate constants in each mixed base suppository, suggesting that these solid fats could regulate the drug release from the mixed base suppositories by changing their viscosity1.

The dissolution and disintegration of the corresponding suppositories showed that the physico–chemical properties and the fraction of incorporated drug together with the lipophilic / hydrophilic nature of the base were important factors. samarium oxide( Sm2 O3) increased the disintegration time of hydrophilic suppositories containing 5-ASA, while the dissolution of both drugs from these formulations remained unchanged2.

The suppositories were prepared using different molecular weight polyethylene glycol in various portions .In contrast with the rapid release of conventional suppositories form, sustain release form chitosan granules were observed. Furthermore, the release rate could be controlled by changing the mixing ratio of drug and chitosan3.

Rheological studies in the pre formulation phase of ethosuximide suppositories to determine the influence of the active ingredient and adjutants on the melting characteristics and rheological performance of the suppositories. Both types of studies were performed on the fatty bases witepsol H-19 and suppocire AP, each mixed with 5% w/w polysorbate 80, 0.1% w/w docusate sodium and 3% w/w tetranyl AT-1/DP and on the suppository formulations obtained by the addition of 150 mg of ethosuximide to these excipients. Pure lipophilic excipients have two peaks in the DSC curve. The first one occurs at lower temperatures (27.3̊ C for the suppocire AP and 34.3̊ C for the witepsol H19) and the second peak at higher temperatures (36.27 and35.95̊ C for the suppocire AP and witepsol H19, respectively)4.

The bioavailabilities of drugs fromsuppositories are taken into consideration. The factors affecting bioavailability, the avoidance of first-pass effects, the role of absorptpromoters, a sustained-release effect and selected therapeutic indications for the application of suppose5.

The release of mebeverine hydrochloride, in two different strengths 100 and 200 mg, from different suppository bases was studied in-vitro to choose the best base to be used in-vivo. The results showed that the fastest release of the drug was from polyethylene glycol 4000 suppository base. On studying the effects of the suppositories on some spasmogens on the isolated guinea-pig ileum the polyethylene glycol suppository containing 100 mg drug gave zero antagonism to acetyl choline (ACh), histamine and barium chloride (BaC12)6.

To develop the safe formulation that can safely improve bioavailability of poorly absorbable drugs and that is practically available, we prepared the suppositories of rebamipide, a poorly soluble and poorly absorbable antiulcer drug, by employing the combinatorial use of sodium laurate (C12), an absorption enhancer, with taurine (Tau) or l-glutamine (l-Gln), an adjuvant exerting the cytoprotective action. Although the dissolution of rebamipide from fatty base (FB) suppository prepared using Witepsol H-15 was very slow, it was remarkably improved by the addition of C12 and l-Gln or Tau into the suppository7.

To evaluate the efficacy and tolerability of vaginal pessary treatment of vaginitis. The method involved in phase-3 studies using one vaginal pessary the reduction occurred in symptoms and signs of vaginitis the gynecological and microbiological evaluation carried out, by using microscopy and candida albicons culture. The combination of metronidazole and miconazole treatment of the most common causes of vaginitis8.

Extensively used beta- lactam antibiotics and 5- nitro imidazole used anaerobic bacteria antibiotic resistance gram negative bacilli of beta- lactam classified as 1) production 2) alteration 3) changes in outer membrane permeability. The 5- nitroimidazole molecule reduction of nitro group in the absence of oxygen the identified in bacteroides fragilis group spp. The mechanism of resistance is critical for both the selection of antimicrobial therapy and the design of new antimicrobial agents. To review the mechanisms for and the prevalence of beta-lactam and metronidazole resistance in strain belonging to the B. Fragi9.

The suppositories properties mainly depend the properties of bases. These bases properties mainly affect the formulation and evaluation of the suppositories10.

6.3
7
7.1 / OBJECTIVE OF THE STUDY:-
The objectives of the study is as follows:
1) The current study is to develop an ideal rectal drug delivery system.
2) Formulation of suppositories by suitable method.
3) Characterisation of formulated suppositories.
4) Evaluation of suppositories for their physicochemical studies.
5) Stability studies for selected formulations.
MATERIALS & METHODS:-
SOURCE OF DATA:-
. Review of literature resourced from:
Journal such as
. Indian journal of pharmaceutical sciences
. Journal of controlled release
. Indian drugs
. Science direct
Websites:
•World Wide Web.
•J-Gate@Helinet
•Science Direct
•Khup.com
•Wikipedia
7.2
7.3
7.4
7.5
7.6
8 /
Method of collection of data (including sampling procedures if any):
The data will be collected from prepared formulations subjected to different evaluation techniques and stability studies obtained from ICH guidelines.

Materials
Anti histamine drug and bases will be procured / obtained from Pharma grade suitable manufacturer. All the other reagents will be of analytical grade.
[[
Methods
1) Preparation of suppositories by hot melting.
2) Thermal analysis.
3) Evaluation
a)Visual evaluation.
b)Melting point.
c) Liquefaction time.
d)Mechanical strength.
e)Solidification.
f)Drug release studies.
g) Stability studies.
Does the study require any investigation or interventions to beconducted on patients or other humans or animals?
- Not Applicable-

Has ethical clearance been obtained from your institution in case of7.5?
-Not Applicable -
LIST OF REFERENCES:-

Toshihito T, Norihito S, Kazutaka H, Toshikiro K. Evaluation of sustained release suppositories prepared with fatty base including solid fats with high melting points. Int J Pharm 2004;278:275–82.

Sayeh FA, Sverre AS, Tor W, Christina G. Influence of neutron activation factors on the physico–chemical properties of suppositories and their excipients. Eur J Pharm Sci 1999;8:193-201.

Nilfifer T, Dilek E. Sustained release characteristics and pharmacokinetic parametersof ketoprofen suppositories using chitosan. Int J Pharm 1997;147:71-7.

Margarit MV, Caballero JD. Thermal and rheological study of lipophilic ethosuximide suppositories. Eur J Pharm Sci 2003;19:123-8.

Hermann TW. Bioavailability of drugs from suppositories. Int J pharm 1995Jan30;123:1-11.

Ehab AH, Seham S, Abdel H, Kamal EH, El T. Formulation, in-vitro release and ex-vivo spasmolytic effects of mebeverine hydrochloride suppositories containing polycarbophil or polysorbate 80. Int J Pharm 1996Oct11;142(2):163-8.

Masateru M, et al. Development of suppository formulation safely improving rectal absorption of rebamipide, a poorly absorbable drug, by utilizing sodium laurate and taurine. J Controlled Release 2004Sep14;99(1):63-71.

Fabio P, Aroldo C, Geraldo D, Iara L, Luis B, Alvaro P. Metronidazole and miconazole nitrate in treatment of vaginitis. Int J Gynaecol obstet 2008 April10;102:287-92.

Hong F, Charlotta E, Maria H, Carlerik N. Metronidazole resistant bacteroides fragilis group. Int J Antimicrob Agents 2002Feb12;19:361-70.

Lieberman A. Pharmaceutical dosage forms: Edited by Rieger M, Banker S, Martin, Gilberts. Disperse system. Second ed. New York Academic Press 2005;p:446-96.

9 / Signature of the Candidate / (PRAVEEN KUMAR SINGH)
10 / Remarks of the Guide: / The topic selected for dissertation is satisfactory. Adequate equipments and chemicals are available to carry out the project work
11 / Name And Designation
11.1 / Guide / MR. RAJARAJAN.S
ASST. PROFFESOR DEPARTMENTOF PHARMACEUTICS
KARNATAKA COLLEGE OF PHARMACY
#33/2, THIRUMENHALLI
HEGDE NAGAR MAIN ROAD
BENGALURU-64
11.2 / Signature of the Guide / ( MR. RAJARAJAN.S)
11.3 / Co- Guide / -NOT APPLICABLE-
11.4 / Signature of the Co- Guide / -NOT APPLICABLE-
11.5 / Head of the Department / DR.K.RAMESH
HOD OF PHARMACEUTICS
KARNATAKA COLLEGE OF PHARMACY
#33/2,THIRUMENHALLI
HEGDE NAGAR MAIN ROAD
BENGALURU-64
11.6 / Signature of the HOD / (Dr. K.RAMESH)
12 / 12.1 / Remarks of the Principal / All the required facilities will be provided to carry out dissertation work under the supervision of the Guide.
12.2 / Principal / DR.K. RAMESH.
PRINCIPAL & HOD OF PHARMACEUTICS
KARNATAKA COLLEGE OF PHARMACY
#33/2, THIRUMENHALLI
HEGDE NAGAR MAIN ROAD
BENGALURU-64.
12.3 / Signature of the Principal / (DR.K.RAMESH)