RAJIV GANDHIUNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA.

ANNEXURE- II

PROFORMA FOR REGISTRATION OF SUBJECT FOR

DISSERTATION

1. / Name of the Candidate and Address: / PRAVEEN GOLASANGI
GovernmentCollege Of Pharmacy Hostel,
# 2 , P Kalinga Rao road , Subbaiah Circle,
Bangalore-560027
2. / Name of the Institute: / GovernmentCollege of Pharmacy.
Bangalore-560 027
3. / Course of Study and Subject: /

Master of Pharmacy in Pharmaceutics

4. / Date of admission to course / 25 JULY 2011
5. / Title of the Topic:
“PREPARATION AND EVALUATION OF FLOATING BEADS AS A CHRONOTHERAPEUTIC APPROACH FOR THE TREATMENT OF ULCER”
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11. / Brief Resume of Intended Work:
6.1: Need for the Study:
Chronopharmaceutics is a branch of pharmaceutics(science and technology of drug dosage forms) deals with the designand evaluation of drug delivery systems that release a bioactive agent at arhythm that ideally matches in real time, the biological requirement of a givendisease therapy or prevention.
Chronotherapy is theadministration of drugs at times at which they are most effective and best tolerated. The chronotherapy of a medication may be
accomplished by the appropriate timing of conventionally formulated tablets
capsules, and a special drug delivery system to synchronize drug
concentrations torhythms in disease activity.
The chronopharmacotherapy has been applied for various diseases like
asthma, hypertension, peptic ulcer and arthritis showcircardian variation,
which demands time-scheduled drug release for effective action.Circadian,
wordcomes from Latin word “circa” means about and “dies” means day.
Normal gastric acid secretion follows a circadian rhythm with asudden
surge of gastric acidity when gastric pH level goes far below4 between
midnight and 2 am.
H2-antagonists (ranitidine, famotidine and nizatidine) are the drugs of choice for the treatment of peptic ulcer. Further colonic metabolism of H2-antagonists favour the gastroretentive dosage forms.Hence the present study is planned to prepare and optimize gastroretentive beads by using selected H2-antagonist and polymers to release the drug atthedesired time.
6.2: Review of literature
Akihiko Kikucho, Minako Kawabuchi, Masayasu Suhihara, Yasuhisa Sakurai, Teruo Okano*have prepared calcium alginate beads by using sodium alginate along with calcium ions in aqueous solution. Using the alginate dissolution mechanism, the macromolecular dextran was released in a pulsatile manner. The lag time could be controlled by either alginate molecular weight, alginate concentration in the preparation, or gel beads size. The larger the diameter of the alginate gel beads, the later the observed release time onset. Thereafter dextran was released without changing release rate. Furthermore, they have succeeded to release dextran in a pulsatile fashion using calcium-alginate gel beads by mixing different bead sizes.
T. Bussemer, R. Bodmeier*have developed and evaluated a rupturable pulsatile drug delivery system based on soft gelatin capsuleswith or without a swelling layer and an external water-insoluble but -permeable polymer coating, which released the drug aftera lag time (rupturing of the external polymer coating). Typical pulsatile drug release profiles were obtained atlower polymer coating levels, while the release was slower and incomplete at the higher coating levels. CAP-coated capsulesresulted in a more complete release than EC-coated capsules.
Srisagul Sungthongjeena, Satit Puttipipatkhachorna*, Ornlaksana Paeratakulc,Andrei Dashevskyb, Roland Bodmeierb have designed a tablet system consisting of cores coated with two layers of swelling and rupturable coatings and evaluated aspulsatile drug delivery system. Cores containing buflomedil HCl as model drug were prepared by direct compression of
different ratios of spray-dried lactose and microcrystalline cellulose and were then coated sequentially with an inner swellinglayer containing a superdisintegrant (croscarmellose sodium) and an outer rupturable layer of ethylcellulose. The lag
time of the pulsatilerelease tablets decreased with increasing amount of microcrystalline cellulose in the cores and increased with increasing levelsof both swelling layer and rupturable ethylcellulose coating. Increasing levels of the ethylcellulose coating retarded the wateruptake and thus prolonged the lag time.
Pasquale Del Gaudio* , Paolo Colombo,Gaia Colombo, Paola Russo, Fabio
Sonvico have prepared sodium alginate beads by laminar jet break-up technology. The effect of polymer concentration, viscosity and polymeric solution flow rate on the characteristics of beads was studied.The re-hydration kinetics of dried beads in simulated gastric fluid (SGF) showed that the maximum swelling of beads was reached after 1–2 h, with an increase in volume of two to three times and a time lag dependent on the polymer concentration. The re-hydration swelling profiles in simulated intestinal fluid (SIF) showed no time lag and higher swelling volume; moreover, in this medium after the maximum swelling was reached, the bead structure was quickly disaggregated.
Andrei Dashevsky*, Ahmad Mohamad developed and evaluated a pulsatile multiparticulate drug delivery system (DDS), coated with aqueous dispersionAquacoat® ECD. A rupturable pulsatile drug delivery system consists of (i) a drug core; (ii) a swelling layer, comprising a superdisintegrant anda binder; and (iii) an insoluble, water-permeable polymeric coating. Upon water ingress, the swellable layer expanded, resulting in the rupturing ofouter membrane with subsequent rapid drug release.
Shraddha S. Badve, Praveen Sher, Aruna Korde, Atmaram P. Pawar*, have prepared hollow calcium pectinate beads for floating-pulsatile release of diclofenac sodium intendedfor chronopharmacotherapy. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase
followed by a burst release. To overcome limitations of various approaches for
imparting buoyancy, hollow/porous beads were preparedby simple process of acid-
base reaction during ionotropic crosslinking. The floating beads obtained were porous (34% porosity), hollowwith bulk density <1 and had Ft50% of 14–24 h.The floating beads provided expected two-phase release pattern with initial lag time during floating in acidic mediumfollowed by rapid pulse release in phosphate buffer. This approach suggested the use of hollow calcium pectinate microparticles as promisingfloating-pulsatile drug delivery system for site- and time-specific release of drugs acting as per chronotherapy of diseases.
Frances Stops*, John T. Fell, John H. Collett, Luigi G. Martini have preparedfloating calcium alginate beads, designed to improve drugbioavailability from oral preparations and compared with that from many commerciallyavailable and modified release products. A model drug, riboflavin, was alsoincorporated into the formula. Physical properties of the calcium alginate beads were investigated. Using SEM and ESEM, externally the calcium alginate beads were sphericalin shape, and internally, air filled cavities were present thereby enabling floatation of the beads. Riboflavin release from the calcium alginate beads showed that riboflavin release was slow in acidic media, whilst in more alkali media, riboflavin release was more rapid.
Pallab Roy, Aliasgar Shahiwala* have designed a programmed delivery of ranitidine hydrochloride from a floating tablet withtime-lagged coating. In thisstudy, investigation of the functionality of the outer polymer coating to predictlag time
and drug release was statistically analyzed using the response surface methodology (RSM).RSM was employed for designing of the experiment, generation of
mathematical models and optimizationstudy. The chosen independentvariables, i.e. percentageweight ratios of ethyl cellulose to hydroxypropylmethyl cellulose in the coating formulation and coating level (% weight gain) were optimized with a32 full
factorial design.
Patel R.P*, Baria A.H , Pandya N.B. have prepared calcium alginate beads containing water-soluble drugFamotidine. A multiple-unit-type oral floating dosage
form of famotidine was developed to prolong gastric residence time,target peptic ulcer and increase drug bioavailability. The evolvinggas permeated through the alginate matrix, leaving gas bubbles or pores, which provided the beads buoyancy. The preparedbeads were evaluated for percent drug loading, drug entrapment efficiency, buoyancy and in vitro release. The formulationswere optimized for different weight ratios of gas-forming agent and sodium alginate.
J. Zhang, Q. Wanga, A. Wang*found a new way to slow down the release of drugs and to solve the burst release problem ofdrugs from traditionally used hydrogel matrices, a series of novel pH-sensitive sodium alginate/hydroxyapatite
(SA/HA) nanocomposite beads was prepared by the in situ generation of HA micro-particles in thebeads during the sol–gel transition process of SA play. The factors influencing the swelling behaviour, drug loadingand controlled release behavior of the SA/HA nanocomposite beads were also investigated usingdiclofenac sodium (DS) as the model drug. The HA micro-particles act as inorganic crosslinkers in the
nanocomposites, which could contract and restrict the movability of the SA polymer chains, and thenchange the surface morphology and decrease the swell ratio. Meanwhile, the entrapment efficiency ofDS was improved, and the burst release of DS was overcome.
Sangeetha S*, Sakthisarvanan V, Komala M, Harish G, Sivakumar Vhave designed gastroretentive beads of theophylline by ionotropic gelation and was
formulated in two different combinations such as sodium alginate along withguar gum and sodium alginate with hydroxy ethyl cellulose. The gas forming agent’s calcium carbonate was also added in four differentconcentrations. The formulated beads were then evaluated for particle size, drug content, floating properties and invitro dissolution.
6.3 Main objective of the study:
The present work is an attempt,
  • To formulate floating pulsatile microbeads containing a selected
H2-antagonist.
  • Preparation of floating microbeads:
The floating microbeads can be prepared by the following method:
  • Ionotropic gelation method
  • Evaluation of the formulation consists of:
Size analysis
Determination of porosity and bulk density
Drug content
Buoyancy test (Floating test)
Crushing strength
Moisture content
Scanning electron microscopy
Infrared spectroscopy
Stability studies on the selected formulations as per ICH guidelines.
Dissolution studies
Materials & Methods:
Drug; AH2-antagonist( Ranitidine, Famotidine, Nizatidine etc.) will be selected.
Polymers and excipients; Calcium carbonate, Sodium alginate,Crospovidone,
pectin, guar gum, chitosan, HPMC,Hydroxy ethyl cellulose, anhydrous citric acidetc.
Solvents; Acetic acid, Ethanol etc..
7.1 Source of the data:
The data required for the work will be collected from different books , Journals
and articles available in the Library of Govt. college of Pharmacy, Journals
available at Jgate – Helinet of the Rajiv Gandhi University of Health sciences
Website and through various internet sources.
7.2 Method of collection of data:
The data will be collected by subjecting the prepared floating microbeads to different evaluation parameters as cited under 6.3.
7.3 Does the study require any investigations or interventions to be
Conducted on patients or other humans or animals? If so, please
Describe in brief.
Not applicable
7.4 Has ethical clearance been obtained from your institute in case 7.3?
Not applicable.
List of references:
  1. Akihiko kikuchi, Minako kawabuchi, Masayasu Sugihara, Yasuhisa sakurai, Teruo okano.Pulsed dextran releas from calcium-alginate beads.Jounal of Controlled Release 1997;47;21-29
  2. T. Bussemer, R. Bodmeier.Formulation parameters affecting the performance coated gelatine with pulsatile release profiles. International journal of pharmaceutics 2003;267;59-68
  3. Srisagul Sungthongjeen, Satit Puttipipatkhachorn, Ornlaksana Paeratakul, Andrei Dashevsky, Roland Bodmeier. Development of pulsatile release tablets with swelling and rupturable layers. Journal of Controlled release 2004;95;147-159
  4. Pasquale Del Gaudio, Paolo Colombo, Gaia Colombo, Paola Russo, Fabio Sonvico.Mechanisms of formation and disintegration of alginate beads obtained by prilling. International journal of pharmaceutics 2005;302;1-9
  5. Andrei Dashevsky, Ahmad Mohamad.Development of pulsatile multiparticulate drug delivery system coated with aqueous dispersion Aquacoat. International journal of pharmaceutics 2006;318;124-131
  6. Shraddha S. Badve, Praveen Sher, Aruna Korde, Atmaram P. Pawar.Development of hollow/porous calcium pectinate beads forfloating-pulsatile drug delivery. European Journal of Pharmaceutics and Biopharmaceutics 2007;65;85-93
  7. Frances Stops, John T. Fell, John H. Collett, Luigi G. Martini.Floating dosage forms to prolong gastro-retention—Thecharacterisation of calcium
alginate beads.International Journal of Pharmaceutics 2008;350;301-311
  1. Pallab Roy, Aliasgar Shahiwala.Statistical optimization of ranitidine HCl floating pulsatile delivery system forchronotherapy of nocturnal acid breakthrough. European Journal of Pharmaceutical Sciences 2009; 37; 363–369
  2. Patel R.P., Baria A.H., Pandya N.B.Stomach-specific Drug Delivery of Famotidine usingFloating Alginate beads. International Journal of PharmTech 2009; 1; 288-291
  3. J.Zhang, Q.Wanga, A.Wang.In situ generation of sodium alginate/hydroxyapatite nanocomposite beads asdrug-controlled release matrices. Acta Biomaterialia 2010; 6; 445-454
  4. Sangeetha S, Sakthisarvanan V, Komala M, Harish G, Sivakumar V.Design and Evaluation of Gastroretentive beads of Theophylline by Ionotropic Gelation. International Journal of Pharmacy and Pharmaceutical Sciences 2010;1; 101

9. / Signature of the Candidate: / (PRAVEEN GOLASANGI)
10. / Remarks of the Guide:
11. / Name and Designation of:
11.1 Guide:
11.2 Signature: / Dr. Vijaya G Joshi
PROFESSOR,
DEPT. OF PHARMACEUTICS,
GOVT.COLLEGE OF PHARMACY,
# 2, P.KALINGA RAO ROAD, SUBBAIAH CIRCLE,
BANGALORE –560 027
11.3 Co-guide:
11.4 Signature: / NOT APPLICABLE
NOT APPLICABLE
11.5 Head of the Department:
11.6Signature: / Dr. N.G. NANJUNDASWAMY,
PROFESSOR,
DEPT. OF PHARMACEUTICS,
GOVT.COLLEGE OF PHARMACY,
BANGALORE –5600 27.
12. / 12.1 Remarks of the principal:
12.2 Signature: Dr.S.SHASHIDHARA
PRINCIPAL,
GOVTCOLLEGE OF PHARMACY,
BANGALORE-27