FORMULATION AND EVALUATION OF GASTRIC FLOATING

ALGINATE BEADS OF ANTI RETROVIRAL DRUG

M.PHARM DISSERTATION PROTOCOL

SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

KARNATAKA

BY

B.RAJIV DINAKAR BABU

I M.PHARM

UNDER GUIDANCE OF

MRS.BENY BABY

ASSISTANT PROFESSOR

DEPARTMENT OF PHARMACEUTICS

KARNATAKA COLLEGE OF PHARMACY

BENGALURU-560064

(2011-2012)

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA, BENGALURU

ANNEXURE –II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1 /

Nameof the Candidate and Address

/ B. RAJIV DINAKAR BABU
Karnataka College Of Pharmacy
# 33/2 Thirumenahalli
Hegde Nagar Main Road
Bengaluru-560064.
PERMANENT ADDRESSS
S/O B.THOMAS,
MIG 186,APHB colony,
Adoni,Kurnool D.T, PIN 518302.
ANDHRA PRADESH.
2 /

Name of the Institution

/ Karnataka College Of Pharmacy
# 33/2 Thirumenahalli
Hegde Nagar Main Road
Bengaluru-560064.
3 /

Course of Study and Subject

/

MASTER OF PHARMACY (PHARMACEUTICS)

4

5 /

Date of the Admission

Title of the Topic :

/ 13th July 2011
“FORMULATION AND EVALUATION OF GASTRIC FLOATING ALGINATE BEADS OFANTI RETROVIRAL DRUG”
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8 / Brief resume of the intended work:
Need for the study
The GFDDS of present investigation are designed to retain in the stomach for longer periods of time and to deliver the drug effectively to the more absorptive regions of the upper parts of the small intestine. The system provides increased absorption at a rate such that effective plasma levels are maintained for prolonged duration.
The pharmaceutical formulation in the form of floating alginate microspheres comprises an effervescent agent, calcium chloride and sodium alginate. When calcium ions are added to a sodium alginate solution, alignment of the G blocks occurs; and the calcium ions are bound between the two chains like eggs in an egg box. Thus the calcium reactivity of algins is the result of calcium-induced dimeric association of the G block regions.
Upon contact with gastric fluids, the polymer forms a hydrated gel matrix and entraps the gas generated by the combination of effervescent agent. The combination of effervescent agent and swell able polymer permits the system to float in the stomach. Additionally the gel forming polymer produces a cross linked three dimensional molecular networks resulting in a “Hydrodynamically balanced system” that is retained in the stomach and releases the drug over a prolonged period of time.
The current research is focused to have the controlledrelease floating alginate microspheres for prolonged drug release.
Review of the literature
Developed an HBS system containing a homogeneous mixture of drug and the hydrocolloid in a capsule, which upon contact with gastric fluid acquired and maintained a bulk density of less than 1 thereby being buoyant on the gastric contents of stomach until all the drug was released.1
Buoyant controlled release powder formulation, which may be either filled into capsules or compressed into tablets. The formulation consists of a drug of basic character, a ph dependent polymer, which were a water soluble salt of alginic acid and a ph independent hydrocolloid gelling agent (such as HPMC, Methyl cellulose or hydroxyl propylcellulose) and binder. Other authors have also prepared tablets with alginic and HPMC that were able to float on gastric contents and provided sustained release characteristics.2
Presented different examples of floating force kinetics obtained from polymeric matrix floating forms. The floating curves showed that the bulk density of a dosage form is not most appropriate parameter for describing its buoyancy capabilities. These capabilities are however preferably represented and monitored by resultant weight measurements.3
Developed gentamycin sulphate SR tablets based on the hydrodynamically balanced system and performed dissolution study by rotary basket method and found first order release4 kinetics with the dissolution rate constant of 0.3992hr-1.
Aime Aimed at pharmacokinetic and hemodynamic effects of diltiazem floating tablets in 8 healthy volunteers and found that the duration of hypotension was longer with floating tablets than with the normal ones.5
Developed a new drug delivery system of sotalol. In the formulation of this system both the concepts of adhesiveness and of floatation were applied to increase the gastric residence time. 6
Developed a sustained release dosage form. It comprises of a bilayer formulation in which one layer consisted of drug mysoprostoland other had a floating layer. The dosage form remained buoyant for about 13 hours.7
Presented a new approach based on a three layer matrix technology to control drug release for oral administration and compressed polyethylene oxide together with theophylline and other excipients into three layer asymmetric floatable systems. Results showed that during 16 hrs dissolution study drug is completely released following the zero order kinetics with no burst effect.8
Incorporated nimodipine into poloxamer 188 solid dispersion before formulation, and then mixed the excipient. The solid dispersion was directly compressed into nimodipine floating sustained release tablet and in vitro release confirmed to zero order kinetics.9
Studied the drug release mechanism of xanthan gum and karaya gum matrices to control the release of varying properties of two model drugs caffeine and diclofenac sodium. They reported that karaya gum displayed a much lower hydration capacity and a higher rate of erosion. Karaya gum produced near zero order release with the erosion mechanism playing a dominant role.10
Have a disadvantage of a release all or nothing emptying process while the multiple unit particulate system pass through the GIT to avoid the vagaries of gastric emptying and thus release the drug more uniformly. Various approaches have been worked out to improve the retention of oral dosage form in the stomach.11
Main objective of the study:
The objective of the study is as follows:
  • The current study is to develop ideal Floating alginate beads.
  • Formulation ofalginate beads by suitable method.
  • Evaluation ofalginate beadsfor their physicochemical studies.
  • In vitro dissolution studies.
  • It would be capable of reducing the frequency of administration and the dose-dependent side effects associated with the repeated administration of conventional tablets.
Materials and Methods:
Source of data
Review of literature from:
Journals such as
  • International Journal of Pharmaceutics
  • Indian Journal of Pharmaceutical Sciences
  • Journal of Controlled Release
  • Indian Drugs
Web sites :
  • World Wide Web.
  • Science direct.
  • J-Gate@Helinet.
Materials
Anti retroviraland Polymers will be procured from suitable Pharma grade
Manufacturer. Other reagents will be of analytical grade.
Methods
1. Formulation of floating alginate microspheres using sodium alginate and HPMC.
2. Evaluation of floating alginate beads.
a)Preparation of calibration curve of drug in 0.01N HCl.
b)To evaluate the floating microspheres for
  1. Percentage yield and drug entrapment efficiency.
  2. Particle size
  3. In vitro dissolution studies of prepared floating alginate microspheres.
  4. In vitro drug release kinetics.
  1. Floating behavior.
  2. Floating lag time.
3. Stability studies of the optimized formulation.
Method of collection of data (Including sampling procedures if any):
The data will be collected from prepared formulations subjected to different evaluation techniques, scale-up techniques and stability studies obtained from ICH guidelines.
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Does the study require any investigation or interventions to be conducted on patients or other humans?
NOT APPLICABLE

Has ethical clearance been obtained from your institution in case of 7.5?
NOT APPLICABLE
List of References
  1. Sheth PR,Tossounian. Sustained release pharmaceutical capsules. US Patent 41978 November21;126-672.
  1. Timmins P, Lee K, Dennis A. Sustained release pharmaceutical capsules. US Patent 5 1992 December 8:169;638.
  2. Timmermans J,Moes V. How well do floating dosage form float Int J Pharm 62:207-216.
  3. Xu WL,TuXD.Development of gentamycin sulphate sustained release tablet remaining floating in stomach. Yao Xue Xue Bao1992;26(7):541-5.
  4. Gu, J.H, Chen SX, Zhu J.B.Pharmacokinetics and pharmacodynamics of diltiazem floating tablets. Zhongguo Yao Li Xue Bao 1992;13(6):527-37.
  5. Jimenez–Castelanos MR, Zia H Rhodes CT. Design and testing in-vitro of a bioadhesive and floating drug delivery system for oral application.Int J Pharm 1994;105:65-70.
  6. Micheal R Franz MR, Marianne P. Sustained release, bilayer buoyant dosage form. US Patent 51993 August 3;232:704.
  7. Yang L, Fasihi R.Zero order release kinetics from a self correcting floatable asymmetric configuration drug delivery system. J Pharm Sci 1996;85:10-3
  8. Wu W, Zhou Q , Zhang HB. Studies on nimodipine sustained release tablet capable of floating on gastric fluids. Yao Xue Xue Bao1997;32(10):786-90.
  9. Dale L, Munday, Philip J.Int J Pharm 2000;203:179-92.
  10. Punam Gaba, Monika Gaba. Floating microspheres. 2008 Pharmainfo.net.

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