Review of Literature

2.1 Review on floating drug delivery systems formulation

Singh et al.1 dealt with current mechanical degrees of progress of FDDS including approved

development frameworks and propelled things, and their focal centers and future potential for

oral controlled solution transport was assessed.

Dave et al.2 dealt with gastroretentive pharmaceutical improvement procedure of ranitidine

hydrochloride. Guar gum, xanthan gum, and hydroxypropyl methylcellulose were looked into for

gel-forming properties. Sodium bicarbonate was entwined as gas-creation administrators. The

effects of citrus center and stearic perilous on cure release profile and skimming properties were

analyzed. These studies demonstrate that best conceivable kind disposition between release rate

enhancer and release rate retardant can make pharmaceutical isolating profile like speculative

disintegrating profile.

Soppimath et al.3 tended to quickly physiology of gastric discharging framework concerning

floating arrangement development structures. As of late, multiparticulate drug-development

frameworks are utilized as bit of oral transport of solutions. One of methods toward this

objective is to build up drifting microspheres to broaden gastric bolster time.

Baumgartener et al.4 prepered floating grid tablets with high measurements of openly

dissolvable drigs. Tablets containing HPMC, drug and diverse added substances are packed.

Tablet piece and mechanical quality have more noteworthy impact on floating properties and

medication discharge. With consolidation of gas creating specialists, other than ideal floating

time of 30 seconds and span of gliding > 8 hr, medication discharge was additionally expanded.

Shimpi et al.5 prepere Gelucire43/01 purpose of outline multi-unit drifting frameworks of

particularly water-dissolvable medication diltiazem HCl. Pretty just around 65% to 80%

arrangement was released over 6 hours with beginning vivacious release from surface. Surface

topography, HSPM, DSC examination of made examples exhibited stage change of Gelucire.

The stage change in like way recognized first extension in game plan release. Considering

everything, hydrophobic lipid, Gelucire 43/01, can be considered as genuine conveyor for

structure of multi-unit floating remedy advancement diagram of by and large water-dissolvable

solutions, for event, diltiazem HCl.

Stochwell et al.6 defined and assessed floating gel framework. Lightness was accomplished via

carbon dioxide gas and its resulting entanglement into gel system. Sodium alginate, which

experiences gelation in acidic conditions and in vicinity of calcium, was utilized. It was assessed

in vitro as managed discharge floating gel framework.

Igani et al.7 planned measurements structure with particular density under one as twofold layer

maintained discharge packed hydrophilic grid to accomplish reproducible floatation of tablet.

Carbon dioxide was caught into gelled hydrocolloids. The gastric maintenance of HBS

measurement structure was discovered to be essentially more than that of non-floating dose

structure.

Sheth et al.8 made regulated discharge hydrodynamically adjusted holders which, upon contact

with gastric liquid got and kept up mass thickness of under one and stayed light in liquid and

remained so until generously large portion of dynamic fixings are discharged. The percent

Chordiazepoxide discharge from cases into reflected gastric liquid (pH 1.2) following 1,2,3.7

hours was 39,61,… 100 % only.

Sangekar et al.9 researched impact of sustenance and particular gravity on gastric upkeep time of

skimming and non-floating tablet purposes of enthusiasm utilizing gama scintigraphy as bit of

people. No affiliation was found between gastric home time and particular gravity of estimation

structure.

Nakamichi et al.10 coordinated floating estimation structure made out of nicardipine

hydrochloride (NH) and hydroxypropylmethylcellulose acidic ruinous determination succinate

(enteric polymer) was readied utilizing twin-screw extruder. By fulfilling position of high-weight

sink fragments energetic region of kick dish outlet, and by controlling barrel temperature, he

found himself organized to set up puffed estimation structure with little and uniform pores. It

was found that porosity and pore purge transversely over could be controlled by fluctuating

measure of calcium phosphate dihydrate. In shaking test, puffed estimations structure was found

to have surprising skimming point of confinement and mechanical quality in hurting system (JP

First Fluid, pH 1.2). The separating profile of NH was controlled by measure of wheat starch. In

separating test utilizing JP Second Fluid (pH 6.8), splendid breaking down of NH and loss of

delicacy were viewed.

Fabregas et al.11 planned long acting acid neutralizer pieces with gliding properties. It contained

substance solvent in water at impartial pH. The plan brought about gastric regularization for

epigastric agony and queasiness.

Mazer et al.12 watched intragastric conduct and ingestion active of ordinary and gliding changed

discharge container of iseradipine under fasted and encouraged conditions. Vicinity or unlucky

deficiency of nourishment as opposed to lightness was main determinant of gastric living

arrangement time of case. The medication discharge and retention were all more by intragastric

association with lipid period of dinner.

Inouye et al.13 arranged light supported discharge granules of Prednisolone utilizing "H" or "L"

evaluations of chitosan. The granules were instantly light in both acidic and nonpartisan liquids.

Supported medication assimilation from these arrangements was seen in beagle canines.

Kawashima et al.14 coordinated void microspheres (microballons) stacked with pharmaceutical

in their outside polymer shell by novel emulsion dissolvable dispersing strategy. The ehanol:

dichloromethane arrangement of pharmaceutical (ibuprofen) what's more, acrylic polymer were

poured that were thermally controlled at 40C. The gas stage made in scattered polymer globule

by spread of dichloromethane confined and inside pit in microballons of polymer. The

flowability and packability of resultant microballons were portrayed by and large property and

arrangement discharge rate were doubtlessly lessened relying on polymer fixation at pH 6.8.

Franz et al.15 arranged supported discharge bilayer light coasting measurements structure

containing Misoprostol, one layer is medication discharge layer and other is light or floating

layer. The measurements structure gave broadened gastric maintenance so that whole medication

is discharged in stomach more than expanded period. The gliding layer incorporated polymer

i.e.HPMC, which has property of gelling and which on contact with gastric liquids, hydrates and

structures thick boundary. This measurements structure is light on gastric liquid for up to more or

less 13 hour.

Desai et al.16 had added to noncompressed controlled release skimming tablets of Thyophylline

using agar and minaral oil. Tablets were made by scrambling medication/minaral oil mix in

warm agar methodology, resultant mix was filled tablet molds which on cooling and air-draying

surrounded floatable CR tablets. The light mineral oil was boss for floating property of tablet

since for the most part high measure of course of action (75%) and low measure of agar (2%)

were used into arrangement.

Du Quing et al.17 figured numerous unit floating managed discharge granules of aminophyllin

and assessed. They have reported that expanding amount of cetyl liquor and octadecanol could

builds granules gliding capacity in vitro.Increased convergance of ethyl cellulose postponed

medication discharge rate.

Whitehead et al.18 prepered gliding alginate globules from alginate arrangement containing

either broke up or suspending Amoxycillin. Medication discharge study demonstrates that

globules arranged with medication in arrangement gave some maintained discharge characters

and these were enhanced by expansion of amylase. The dots held their lightness were amylase

and amoxicilline were consolidated.

Abubakr et al.19 arranged captopril floating and/or bio cement tablets utilizing two evaluations

of HPMC (400 and 15000 cps.).He looked at two traditional tablets; discharge from coasting

tablets was clearly drawn out. A 24 hours controlled discharge measurement structure for

captopril was accomplished. Tablet hardness was discovered deciding element with respect to

lightness of tablets.

Shoufeng et al.20 addresses bona fide trial setup and information examination utilizing reaction

surface framework. A focal composite box-Wilson game plan for controlles passage of calcium

was utilized with three definition variables like HPMC stacking, Citric ruinous stacking and

magnesium stearate stacking. Supported discharge drifting development of calcium with

augmented bioavalability was master.

Farouk et al.21 built up programmable controlled discharge medication transport framework.

The contraption as non edible oral case was design to used regularly worked geometric watch

that keeps gadget skimming in stomach and keep it from encountering straggling leftovers of

GIT.Diferent consistency appraisals of HPMC was utilized as model separating metrixs. Zero-

requesting discharge could be kept up for period taking off between 5 to 20 days going before

geometric impediment was activated off.

Talwar et al.22 arranged gastroretentive oral medication conveyance framework basically

included very permeable lattice having medication, gas creating segment, sugar, discharge

controlling specialists and alternatively spheronising operators. The pharmaceutical detailing

either as pellets, globules, granules or cases was held in stomach while specifically conveying

medication at gastric level or upper piece of small digestive tract for developed time of time.

Joseph et al.23 made drifting sort estimations structure (FDF) of piroxicam in void polycarbonate

(PC) microspheres fit for coasting on reenacted gastric and intestinal fluids was composed by

dissolvable vanishing system. Joining efficiencies of more than 95% were expert for epitome. In

vitro area of piroxicam from PC microspheres into imitated gastric fluid at 37�C exhibited no

principal burst impact. The whole released connected with time for around 8 h after which near

to no was found to be released up to 24 h. In intestinal fluid, release was snappier and

enthusiastic and at high solution payloads, aggregate release came to more than 90% in around 8

h. In vivo assessment of particular estimations sorts of piroxicam, for event, free pharmaceutical,

arrangement exemplified microspheres and microspheres nearby stacking estimation of free cure

in rabbits showed assorted fixing in plasma center time twist proposing enterohepatic transport

of medicaments..

Patel et al.24 made stop dried chitosan polyethylene oxide hydrogel for site-particular serum

toxic substance discharge in stomach. The stop dried PEO framework swollen comprehensively

when showed up diversely in connection to air-dried hydrogels. The stop dried chitosan PEO

could be productive for kept transport of vaccinating specialists harm in acidic environment of

gastric liqud.

Atybi et al.25studied bicarbonate stacked bicarbonate molecule exchange pitch spots secured

with semipermeable layer. The globules showed draw out gastric recidence due to floating.

Despite bicarbonate, model prescription theophyllin has in like manner been stacked on to tar.

This structure gives controlled entry of prescription by covering and has potential application as

control release gastric retentive system.

Yang et al. 26 developed hilter kilter three-layered tablet. The outer layer involved gas creating

system. The other outer layer was similar yet without gas delivering segment. The limit of these

layers was to give crucial gentility and control area of fluid into pharmaceutical containing layer.

Zero-solicitation entry of theophyllin in vitro was workable for 16 hours with softness kept up

through out period.

Timmerman et al.27 enhanced floating and non coasting hydrophilic system case in vitro as to

their delicacy or non daintiness limits and their polar sine evaluation with time. The GRT

prolongation is gotten with floating estimations structure appeared differently in relation to non

floating measurement outlines.

Sheth et al.28 conveyed patent for hydrodynamically change structure. This unit embodying case

definition containing pharmaceutical, hydrocilloid and diverse excipients. After emersion in

other fluid, compartment separate and hydrocolloid outlines hydrated farthest point layer. That

gives definition floating properties. The prescription is in like manner released through this layer

is by spread.

Wei et al.29 figured another sort of two-layer floating tablet for gastric bolster (TFTGR) with

cisapride as model pharmaceutical was made. The in vitro course of action discharge was

resolved, and resultant daintiness and time-social sparkle turn were plotted. As conceded

aftereffect of sodium bicarbonate added to drifting layer, when submerged in imitated gastric

liquid tablet makes and raises to surface, where course of action is little bit at once discharged.

The gameplan segment of this sort of two-layer estimations was controlled by measure of HPMC

in pharmaceutical stacking layer. All around more HPMC, slower pharmaceutical discharges.

Since cisapride has graeter dissolvability in SGF than SIF, in vitro arrangement separating in

SGF is speedier than in SIF.

Soppimath et al.30 made void microspheres out of cellulose acidic ruinous determination stacked

with four cardiovascular pharmaceuticals (Nifedipine, Nicardipine HCl, Varapamil HCl and

Dypiridamole) were empowered by novel dissolvable scrambling dispersal structure. The O/W

emulsion masterminded in watery methodology of 0.05% poly (vinyl liquor) medium with ethyl

acidic harming incitation, water-dissolvable and less ruinous dissolvable, was utilized as

diffusing dissolvable. The yield of microspheres was up to 80%. The microspheres had smooth

surfaces, with free skimming and psyche blowing beating properties. Checking Electron

Microscopy (SEM) affirmed their void structures, with sizes in level of 350-489 mm. The

microspheres were had slant to buoy over gastric media of more than 12 h.

Zia et al.31 advance Sotalol drifting and bioadhesive made discharge tablet showing which

implies gigantic blend of flotation and bioadhesion for drag out living chart in stomach. Another

piece factorial design was utilized to update tablet strategy contaoining 240 mg Sotalol HCl,

level of NaCMC to HPMC and level of EC to Crosspovidone.The subordinate variable was

falling apart, bioadhesive most far off point, tablet withdrawing and obliged weight fource for

going on 6 kg hardness tablets.

Ichiwaka et al.32 supervised skimming granules containing 20% Dextromethorphan HCl,

secured with sodium bicarbonate –HPC-Ethyl liquor blend and vinyl acidic harming finding,

shellac, HPMC phthalate, acetylmonoglyceride, calcium stearate and ethanol blend. The granules

floated in acidic hazardous incitation cushion approach in 14-15 minutes in wake of dousing.

Srivastava et al. 33 prepared floating structure tablets of atenolol to drag out gastric home time

and make drug bioavailability. The tablets were made by direct weight system, using polymers,

for event, HPMC K15M, HPMC K4M, guar gum, sodium CMC, alone or in blend, and other

standard excipients. Tablets were reviewed for physical qualities and for in vitro release

properties for 8 hrs. The effect of getting on society and pharmaceutical release structures were

in like path focused on.

2.2 References

1. Singh, B.N., Kim, K.H., 2000. Floating drug delivery systems: approach to oral controlled

drug delivery via gastric retention. J. Control. Release 63, 235–259.

2. Dave BS, Amin AF, Patel MM. 2004. Gastroretentive Drug Delivery System of Ranitidine

Hydrochloride: Formulation and In Vitro Evaluation. AAPS Pharm Sci Tech., 5(2), article

34.

3. Soppimath KS, Kulkarni AR, Rudzinski WE, Aminabhavi TM. 2001. Microspheres as

floating drug-delivery systems to increase gastric retention of drugs. Drug Metab Rev., 33(2),

149-160.

4. Baumgartner S, Krsti J, Zorko B, 2000. Optimisation of floating matrix tabletand evaluation

of gastric recidence time. Int. J. Pharm., 195(1), 125-135.

5. Shimpi S, Chauhan B, Mahadik K R, Paradkar P, 2004. Preparation and Evaluation of

Diltiazem Hydrochloride-Gelucire 43/01 Floating Granules Prepared by Melt Granulation.

AAPS Pharm Sci Tech., 5(3), 19-25.

6. Stockwell A F, Davis S S, Walker S E, In vitro evaluation of alginate gel systems as sustained

release drug delivery systems. J.Control.Release; 1986, 3: 167-175.

7. Igani H M, Timmermans J, Moes A J, 1987. Conception and in vitro investigation of peroral

sustained release dosage forms with enhanced gastrointestinal transit. Int. J. Pharm., 35, 157-

164.

8. Sheth P R, Tossounian J L, Sustained release pharmaceutical capsules, US patent,

4,126,672,November 21; 1978.

9. Sangejkar W, A Vadino, I Chaudary, A Parr, R Beihn, G Digenis, 1987. Evaluation of effect

of food and specific gravity of tablets on gastric retention time. Int. J. Pharm., 35, 187-191.

10. Nakamichi K, Yasuura H, Fukui H, Oka M, Izumi S, 2001. Evaluation of floating dosage

form of Nicardipine Hydrochloride and Hydroxy propyl methyl cellulose acetate succinate

prepared using twin-screw extruder. Int. J. Pharm., May 7, 218(1-2), 103-112.

11. Fabregas J L, Claramunt J, Cucala J, Pous R, Siles A, 1994. In vitro testing of antcid

formulation with prolong gastric residence time (Amalgate Flot-Coat), Drug. Dev. Ind.

Pharm., 20, 1199-1212.

12. Mazer N, Abisch E, Glffeler J C, Laplanche R, Bauer-frind P, Cucala M, Lukachick M, Blum

A, 1988. Intra gastric gastrointestinal behavior and absorption kinetic of normal and floating

modified release capsule of Iseradipine under fasted and fed conditions. J. Pharm. Sci., 89,

647-657.

13. Inouye K, Machida Y, Sanna T, Nagai T, 1988, Buoyant sustained release tablets based on

chitosan. Drugs Des. Del., 2, 165-175.

14. Kawashima Y, Niwa T, Tekeuchi H, Hino T, Itoh Y, 1992. Hollow microspheres for use as

floating controlled drug delivery system in stomach. J. Pharm. Sci., 81, 135-140.

15. Franz M R, Oth M P, Sustained release bilayer buoyant dosage form, US patent, 5,232,704,

August 3; 1993.

16. Desai S, Bolton S, 1993. A floating controlled drug delivery systems: In vitro in vivo

evaluation. Pharm. Res., 10, 1321-1325.

17. Du Quing, Fan Chum Sun, 1996. Preparation and evaluation of floating granules of

Aminophyllin. Through Chemical Abstract, 125(3), 6745u.

18. Whitehead L, Collette H, 2000. Prolong Gastric retention using floating dosage form. Pharm.

Tech., 3, 82-90.

19. Nur AO, Zhang JS, 2000. Captopril floating /or bioadhesive tablet: Design and release

kinetic. Drug. Dev. Ind. Pharm., 26(9), 965-970.

20. Shoufeng L, 2001. Stastastical Optimization of gastric floating system for oral controlled

delivery of calcium. AAPS Pharm. Sci. Tech., 2(1), 1-10.

21. Farouk M, 1999. A programmable drug delivery system for oral administration. Int. J.

Pharm., 184, 131-139.

22. Talwar N, Sen H, Orally administered controlled drug delivery system providing temporal

and spatial control, WO Patent, 151198; 2000.

23. Joseph N J, Lakshmi S, Jayakrishnan.A A A, 2002. A floating-type oral dosage form for

Piroxicam based on hollow polycarbonate microspheres: in vitro and in vivo evaluation in

rabbits, J. Controlled Release, 79(1), 71-79.

24. Patel V, Amiji M, 1996. Preparation and characterization of freeze dried chitosan Poly

(ethylene oxide) hydrogel for site-specific antibiotic delivery in stomach, Pharm. Res., 13,

588-593.

25. Atyabi, F., Sharma, H.L., Mohammad, H.A.H., Fell, J.T., 1996. In vivo evaluation of novel

gastric retentive formulation based on ion exchange resins. J. Control. Release 42, 105–113.

26. Yang, L., Eshraghi, J., Fassihi, R., 1999. A new intragastric delivery system for treatment of

Helicobacter pylori associated gastric ulcer: in vitro evaluation. J. Control. Release 57, 215–

222.

27. Timmermans J, Gansbeke B Van, Moes A J, 1989. Assising by gama scintigraphy in vivo

buoyancy of dosage form developing known size and floating fource profiles as function of

preparation. Proc, 5th Int. Conf. Pharm. Technol, Vol. I, APGI, Paris, 42-51.

28. Sheth P R, Tossounian J, 1984. Hydrodynamically balanced system (HBS): A novel drug

delivery system for oral use. Drug. Dev. Ind. Pharm., (10), 313-339.

29. Zhenphing Wei, Zhanfeng Yu, 2001. Design and Evaluation of two-layer floating tablets for

gastric retention using cisapride as model drug. Drug. Dev. Ind. Pharm., 27(5), 469-474.

30. Soppimeth Kumeresh, Aminabhavi Tejraj, 2001. Development of hollow microspheres as

floating controlled release systems for cardiovascular drugs: Preparation and release

characteristics. Drug. Dev. Ind. Pharm., 27(6), 507-515.

31. Zia H, Chueth H R, Rhodes C T, 1999. Optimization of Sotalol floating and bioadhesive

extended release tablet formulation. Drug. Dev. Ind. Pharm., 21, 1725-1747.

32. Ichikawa M, Kato T, Kawahara M, Watanabe S, Kayano M, 1991. A new multiple unit oral

floating dosage system. II: In vivo evaluation of floating and sustained release characteristics

with P-amino benzoic acid and Isosorbide Dinitrate as model drugs. J. Pharm. Sci., 80, 1153-

1156

33. Srivastava A. K., Wadhwa Saurabh, Mishra B.205.Oral Sustained Delivery of Atenolol from

Floating Matrix Tablets – Formulation and In Vitro Evaluation. Drug. Dev. Ind. Pharm.,

31(4-5), 367-374

2.3 Review on Ranitidine hydrochloride and its sustain release formulation:

Coffine et al.1 work involved bi-layer, pharmaceutical tablet having one layer figured for quick

discharge (IR) of ranitidine and second layer planned for managed discharge (SR) of ranitidine

with proportion of ranitidine in IR layer to that in SR in scope of from around 30:70 to around

60:40.

Chopra et al.2 innovation identified with gadget for arrival of no less than one dynamic

substance (e.g. ranitidine) into liquid medium by disintegration embodying covering, which is

impermeable to dynamic substance and liquid, having no less than one opening in that and

characterizing molded pit, hole being filled by formed center involving dynamic substance, and

wherein: on introduction of gadget to liquid medium, surface of center is uncovered and

disintegration of surface by liquid medium causes adjustment in no less than one measurement of

territory of surface, while surface zone of uncovered surface remains generously steady over no

less than half of aggregate disintegration time of center; or dynamic substance is arranged in

lattice of latent insoluble excipient, gadget being pivotally symmetrical, with its gap being

incidentally arranged so that discharge surface of center which is uncovered through gap is

significantly round and hollow or piece of chamber fit as fiddle; whereby to permit considerably

consistent arrival of dynamic substance over at any rate piece of disintegration time; and

procedures for its planning.

Mody et al.3 gave oral plans of Ranitidine Hydrochloride as covered tablets and containers

which create controlled or managed disintegration and discharge at genuinely consistent rate

greater than long stretches - length of 12 to 24 hours- - to keep up Ranitidine at coveted levels

over MEC.

Eccentricity et al.4 figured pharmaceutical sythesis for utilization in human or veterinary drug

which embodies ranitidine or physiologically satisfactory salt thereof, alginic corrosive or

physiologically worthy salt thereof, and carbonate or bicarbonate. The structure ideally involves

1.25% to 10% w/w ranitidine hydrochloride, 5% to 35% w/w alginic corrosive, and 2% to 15%

w/w sodium bicarbonate and is ideally as case or tablet. The creations are suitable for treatment

of gastrointestinal issue and especially reflux oesophagitis.

Davis et al.5 figured pieces for oral organization for treatment of gastric issue embodying

histamine H2 receptor foe, and acid neutralizer, ideally cradled to advance nearby assimilation of

H2 receptor opponent, wherein amount of H2 receptor adversary per unit measurement structure

is under 25 mg.

Dave et al.6 composed gastroretentive plan transport methodology of ranitidine hydrochloride.

Guar gum, xanthan gum, and hydroxypropyl methylcellulose were evaluated for gel-including

properties. Sodium bicarbonate was joined as gas-production heads. The effects of citrus center

and stearic perilous on drug release profile and floating properties were investigated. These

studies demonstrate that right suitability between release rate enhancer and release rate retardant

can make answer breaking down profile like speculative rot profile.

Basit et al. 7 surveyed in vitro soundness of ranitidine to colonic microscopic organisms by using

cluster society maturation framework to reenact states of colon. UV and mass spectrometry

examination were finished planned and treated clusters which demonstrated that digestion

system happened by means of cleavage of N–oxide security inside of particle with resultant loss

of oxygen molecule, albeit further metabolic responses are conceivable. Such digestion system

might to limited extent be in charge of small bioavailability of ranitidine as of colon.

2.4 References

1. Coffin; Mark D.; Parr; Alan F. US Patent 5,407,687. Ranitidine solid dosage form, April

1995.

2. Chopra; Sham K.; Nangia; Avinash K.; Lee; David; Molloy; Thomas P. US Patent 5,342,627,

Controlled release device, Aug 1994.

3. Mody; Shri Shirish Bhagwanlal; Doshi; Madhukant Mansukhlal; Joshi; Milind Dattatraya US

Patent 5,853,756, Controlled release formulations of Ranitidine, Dec 1998.

4. Quirk; Christopher W.; Jackson; David A.; Cameron; James M. US Patent 5,456,918,

Ranitidine pharmaceutical compositions, Oct. 1995

5. Davis; Adrian Francis US Patent 5,656,652, Compositions containing histamine H2 receptor

antagonists at low dosage, Aug 1997.

6. Dave BS, Amin AF, Patel MM. 2004. Gastroretentive Drug Delivery System of Ranitidine

Hydrochloride: Formulation and In Vitro Evaluation. AAPS Pharm. Sci.. Tech., 5(2), article

34.

7. Basit Abdul W. and Lacey Larry L., 2001. Colonic metabolism of ranitidine: implications for

its delivery and absorption. Int. J. Pharm. Sci., 227(1-2), 157 – 165.

2.5 Review of work done on low density material

Streubel et al.1 created novel multiparticulate GRDDS and showed its execution in vitro.

Skimming microparticles including (i) polypropylene froth powder; (ii) verapamil HCl as model

pharmaceutical; and (iii) Eudragit RS, ethyl cellulose (EC) or polymethyl methacrylate (PMMA)

as polymers were readied with O in W dissolvable vanishing technique. The microparticles were

whimsical fit as a fiddle and particularly vulnerable. In all cases, magnificent in vitro skimming

conduct was seen.

Streubel et al.2 made and physicochemically delineated single unit, floating controlled remedy

development frameworks including (i) polypropylene froth powder, (ii) system shaping

polymer(s), (iii) drug, and (iv) filler (discretionary). The greatly permeable froth powder gave

low thickness and, along these lines, superb in vitro skimming conduct of tablets. All froth

powder-containing tablets stayed drifting for no under 8 h in 0.1 N HCl at 37 8 C. Unmistakable

sorts of network shaping polymers were centered around: hydroxypropyl methylcellulose

(HPMC), polyacrylates, sodium alginate, corn starch, carrageenan, gum guar and gum arabic.

The tablets separated upon contact with discharge medium, and relative tremendousness of

medication dissipating, polymer swelling and tablet disintegrating for coming about discharge

arranges shifted as a rule sense with sort of grid past. The discharge rate could adequately be

changed by moving ''framework shaping polymer/froth powder'' degree, starting medication

stacking, tablet geometry (compass and stature), sort of cross area framing polymer, utilization of

polymer mixes and advancement of water-dissolvable or water-insoluble fillers, (for case, lactose

or microcrystalline cellulose). The drifting conduct of low thickness medication transport

frameworks could sufficiently be united with accurate control of pharmaceutical discharge

traces.

2.6 References

1. Streubel A., Siepmann J., Bodmeier R., 2002. Floating microparticles based on low density

foam powder, Int. J. Pharm., 241, 279–292.

2. Streubel A., Siepmann J., Bodmeier R., 2003. Floating matrix tablets based on low density

foam powder: effects of formulation and processing parameters on drug release, European

Journal of Pharmaceutical Sciences, 18, 37–45.

2.1 Review of work done of floating microspheres

Haznedar S. et al1 dealt with and surveyed Eudragit (RS and RL) microspheres containing

acetazolamide. Microspheres were masterminded by dissolvable dissipating technique using

CH3)2CO/liquid paraffin structure. The effect of definition portions (mixing pace, polymer:drug

degree, sort of polymer, level of blend of polymers) on atom size, embodiment capacity and in

vitro release properties of microspheres were analyzed. The yields clearly of action and

embodiment efficiencies were high for all reasons of interest microspheres were gotten. Mean

atom size changed by changing polymer: drug degree or blending rate of structure.

Obeidat W. M. et al2 combined pitifully acidic, stomach disturbing piroxicam and weakly

preeminent to unprejudiced, obliged recovering once-over theophylline into structure

microspheres using Eudragit S 100 at tantamount polymer diagram center and medicine

obsession and after that evaluated encapsulation reasonableness and microsphere properties

especially their morphology and isolating properties in differentiating pH media. Optical light

microscopy was used to see microsphere shape. In vitro isolating studies were done on

microspheres at 37oC at 100 rpm with USP breaking down mechanical get-together II using

framework for enteric-secured things at two component distinctive pH media (1.2 and 6.5).Both

outlines show beginning enthusiastic release in acidic medium with theophylline showing more

development in total released in midst of this stage.

Al-Kassas R. et al3 added to conditions obviously of activity of gentamicin sulfate microspheres

with high arrangement stacking and particle gage under 5 µm, using twofold emulsion-

dissolvable spread structure, expected for intraocular connection are portrayed. The microspheres

were prepared from poly methacrylate (Eudragit RS and RL) polymers cross-joined with

polyvinyl alcohol. The parameters that upgraded establishing adequacy of gentamicin in

microspheres and controlled particle size and surface morphology were analyzed. Changing

assistant liquid stage by mostly submerging it with varying centralizations of either KCl or

gentamicin widened union advantage of medication and affected mean widths of microspheres

Sato Y. et al4 made Microballoons (MB) having round demoralization encased inside of hard

polymer shell as estimation structure depicted by mind blowing delicacy in stomach. MB were

planned by emulsion dissolvable dispersal procedure utilizing enteric acrylic polymers isolated

as bit of blend of dichloromethane and ethanol. MB sorted out by blending it with

hydroxypropylmethylcellulose (HPMC) in varying degree, acknowledges updated riboflavin-

discharge properties. These MB were assessed in vivo by examination of urinary arrival of

riboflavin. Thus, solid affiliations were seen between daintiness and discharge half-life (t1/2) and

between riboflavin discharge from MB and aggregate urinary discharge.

Sato Y. et al 5 made Hollow microspheres (microballoons) floatable in JPX III No.1 diagram as

estimation structure delineated by conspicuous light properties in stomach. Microballoons were

arranged by emulsion dissolvable spread structure utilizing enteric acrylic polymers co-

disintegrated with medicine in mix of dichloromethane and ethanol. The release properties of

five one of a kind cures indicating unmistakable water solubilities (cerebral torment course of

action, salicylic perilous, ethoxybenzamide, indomethacin and riboflavin) got inside

microballoons were examined. Sensitivity of microballoons decreased with creating course of

action release rate. Likewise, by merging polymer, for event, hydroxypropylmethylcellulose

within shell of microballoons, release rate of riboflavin from microballoons could be controlled

while keeping up high social shine.

Sato Y. et al6 made Hollow microspheres (microballoons) floatable on JPXIII No.1 approach as

estimations structure orchestrated drifting in stomach. Void microspheres were designed by

emulsion dissolvable spread framework using enteric acrylic polymers with arrangement in mix

of dichloromethane and ethanol. It was found that sorting out temperature picked movement of

cleft inside microsphere and surface smoothness, picking floatability and drug release rate of

microballoon. The relationship between daintiness of microballoons and their physical

properties, e.g. clear thickness and roundness of microballoons were illuminated.

Yamamoto H.et al7 reported tacrolimus was suitable in coordinating ignitable gut infection

(IBD). In treatment of IBD, oral arrangement development utilizing pH-subordinate polymers is

champion amongst best remedial structures. Eudragit P-4135F, pH-delicate polymer for colonic

transport was utilized to get arranged tacrolimus microparticles utilizing oil/oil emulsification or

oil/water emulsification technique joined with dissolvable extraction or vanishing step.

Notwithstanding way that pH-ward remedy discharge was relative for broad mixed bag of

microspheres, it was for the most part found that encapsulation rates of oil/water frameworks

(extraction 38.8±9.4%; diffusing 56.3±1.9%) were better than oil/oil emulsification (4.8±0.4%).

At pH 7.4, in every practical sense brief discharge (inside of 30 min) was seen..

Dashevsky A. et al8 got pH-self-decision discharge profiles from secured pellets containing

meds with pH-subordinate dissolvability. pH-self-administering passage of crucial model

solution verapamil HCl was refined by covering with blend of reasonable polymer scatterings

Kollicoat® SR 30 D (watery diffusing of polyvinyl acidic destructive induction) and enteric

polymer scattering Kollicoat® MAE 30 DP (fluid scrambling of methacrylic damaging and ethyl

acrylate copolymer; methacrylic ruinous copolymer sort C). The two polymers where related

either as allotted layers (enteric polymer + heightened discharge polymer or other course around)

or as polymer mix. A careful balance of degrees of polymers permitted accomplishment of pH-

self-decision discharge.

Beck R. et al9 organized and arranged new nanoparticle-secured medication stacked inorganic

microparticles by shower drying utilizing diclofenac as remedy model. Past works indicated

framework to dry arrangement stacked polymeric nanoparticles utilizing silicon dioxide as

adjuvant, for most part in present proposition medication is connected with silicon dioxide and

depleted polymeric nanocapsule or nanosphere suspensions were utilized as basic covering.

Eudragit S100 was picked in light of its gastric resistance. Right when diclofenac was utilized as

hydrophilic model, in this salt edge, powders sorted out in two stages (concentrate leading up to

now engineered) demonstrated satisfactory gastroresistance by use of Eudragit S100. The

utilization of diclofenac as hydrophobic model (damaging structure) facilitated to powders

indicating uncommon gastroresistance when nanocapsules and triacetin were utilized.

Kumaresh S et al10 exhibited rapidly physiology of gastric cleansing method concerning gliding

medication conveyance framework systems. Starting late, multiparticulate drug-transport

systems are used as piece of oral movement of medicines. One of strategies toward this goal is to

develop drifting microspheres with specific end goal to extend gastric upkeep time. Such

structures have more great circumstances over single-unit estimations shapes. The change of

coasting microspheres incorporates differing dissolvable dispersal methods to make unfilled

inner focus. The present review addresses plan and depiction of drifting microspheres for peroral

course of association of solution.

Lee J. et al11 masterminded Eudragit® microspheres, to float in gastrointestinal tract, to drag out

gastrointestinal travel time. To enhance their delicacy, non-unsteady oil was added to scattered

stage. Exactly when oil part was not miscible with water, more than 90% was caught within

microspheres and deferred coasting time of microspheres. Differentiated and microspheres

masterminded without non-unsteady oil, release rate of prescription from microspheres was

speedier in all cases attempted, beside microspheres containing mineral oil. The dissolvability of

prescription in non-insecure oil impacted release profiles of medicines. The non-flimsy oil tends

to lessen glass move temperature of orchestrated microspheres and change release profile. The

internal morphology of microspheres was insignificantly particular depending upon caught oil

stage used.

Kumaresh S. et al12 organized Hollow microspheres of cellulose acidic destructive

determination stacked with four cardiovascular arrangements (nifedipine [NFD], nicardapine

hydrochloride [NCD], verapamil hydrochloride [VRP], and dipyridamole [DIP]) by novel

dissolvable disseminating vanishing strategy. The oil-in-water emulsion composed in watery

course of action of 0.05% poly(vinyl liquor) medium with ethyl acidic destructive impelling,

water-dissolvable and less lethal dissolvable, was utilized as scattering dissolvable. The yield of

microspheres was up to 80%. The microspheres had smooth surfaces, with free-spouting and

mind blowing pressing properties. The microspheres had a tendency to buoy over gastric media

for more than 12 h. The section of medications was controlled for more than 8 h. The discharge

essentialness took after varying transport sections relying on strategy for medication particles.

Umamaheshwari R.B. et al13 made skilled pharmaceutical development structures for treatment

of Helicobacter pylori disorder utilizing polycarbonate (PC) floating microspheres as medication

transporters. With completed target to grow counter H. pylori impact of acetohydroxamic

dangerous (AHA), floating PC microspheres, which can stay in gastrointestinal (GI) tract for

made period, were arranged by emulsion (O/W) dissolvable vanishing framework. The impact of

PC fixation on morphology, molecule size, catch productivity and arrangement discharge rate

was thought about. In-vitro studies demanded giant coasting properties of PC microspheres.

Taking all things into account, skimming microspheres all the more plausibly cleared H. pylori

from GI tract than arrangement in context of put off gastric home time happening in perspective

of radiant culture of PC.

Lee J. et al14 orchestrated Floating acrylic sap microspheres with internal unfilled structure by

dissolvable scattering and dissemination framework. The yield of microspheres depended on

upon scattering rate of ethanol and/or isopropile liquor.

Joseph N.J. et al15 coordinated gliding sort estimations structure (FDF) of piroxicam in void

polycarbonate (PC) microspheres composed floating on duplicated gastric and intestinal liquids

by dissolvable scrambling system. Joining efficiencies of more than 95% were master for

exemplification. In vitro meeting up piroxicam from PC microspheres into reenacted gastric

liquid at 37oC demonstrated no immense burst sway. The total discharged stretched out with

time for around 8 h after which close to no was discovered to be discharged up to 24 h. In

intestinal liquid, discharge was snappier and enduring and at high medication payloads, total

discharge came to more than 90% in around 8 h.

Chan L. W. et al16 study explored liquid stage covering methodology to go on polymethyl

methacrylate (PMMA)- secured alginate microspheres. Alginate microspheres with mean

estimation of 85.6µm were prepared using emulsification framework. The alginate microspheres,

as focuses, were then secured with particular sorts of PMMA by liquid stage covering structure.

Release rates of Eudragit RS100-secured microspheres in SGF and SIF were close as rate-

controlling polymer coat was insoluble in both media. Pharmaceutical release from Eudragit

S100-secured microspheres was more strengthened in SGF than in SIF, as eventual outcome of

more clear dissolvability of covering polymer in media with pH more recognizable than 7.0. The

medication release rate was influenced by core:coat degree. Drug release from secured

microspheres was best depicted by Higuchi's square root model.

Jain D. et al17 isolated whether Eudragit S100 microspheres can serve as oral transport for

peptide pharmaceuticals like insulin.Microspheres were readied utilizing water-in oil-in water

emulsion dissolvable dispersing strategy with polysorbate 20 as diffusing specialists in within

fluid stage and polyvinyl liquor (PVA)/polyvinyl pyrrolidone as stabilizer in outside watery

stage. The use of more modest inside fluid stage volume (50 m L) and outside watery stage

volume (25 mL) containing PVA in accumulating structure satisfied most eminent epitome limit.

PVA-balance microspheres having most shocking solution encapsulation discharged 2.5%insulin

at pH 1.0 in 2 hours. In phosphate bolster (pH 7.4), microspheres demonstrated beginning burst

area of 22%in 1 hour with extra 28%release in running with 5 hours. The humbler volumes of

inside and outside watery stage, cut down starting burst discharge. The arrival of pharmaceutical

from microspheres took after Higuchi centrality.

Haznedar S. et al18 dealt with and surveyed Eudragit (RS and RL) microspheres containing

acetazolamide. Microspheres were masterminded by dissolvable dissipating technique using

CH3)2CO/liquid paraffin structure. The effect of definition portions (mixing pace, polymer:drug

degree, sort of polymer, level of blend of polymers) on atom size, embodiment capacity and in

vitro release properties of microspheres were analyzed. The yields clearly of action and

embodiment efficiencies were high for all reasons of interest microspheres were gotten. Mean

atom size changed by changing polymer: drug degree or blending rate of structure.

Obeidat W. M. et al19 combined pitifully acidic, stomach disturbing piroxicam and weakly

preeminent to unprejudiced, obliged recovering once-over theophylline into structure

microspheres using Eudragit S 100 at tantamount polymer diagram center and medicine

obsession and after that evaluated encapsulation reasonableness and microsphere properties

especially their morphology and isolating properties in differentiating pH media. Optical light

microscopy was used to see microsphere shape. In vitro isolating studies were done on

microspheres at 37oC at 100 rpm with USP breaking down mechanical get-together II using

framework for enteric-secured things at two component distinctive pH media (1.2 and 6.5).Both

outlines show beginning enthusiastic release in acidic medium with theophylline showing more

development in total released in midst of this stage.

Al-Kassas R. et al20 added to conditions obviously of activity of gentamicin sulfate

microspheres with high arrangement stacking and particle gage under 5 µm, using twofold

emulsion-dissolvable spread structure, expected for intraocular connection are portrayed. The

microspheres were prepared from poly methacrylate (Eudragit RS and RL) polymers cross-

joined with polyvinyl alcohol. The parameters that upgraded establishing adequacy of

gentamicin in microspheres and controlled particle size and surface morphology were analyzed.

Changing assistant liquid stage by mostly submerging it with varying centralizations of either

KCl or gentamicin widened union advantage of medication and affected mean widths of

microspheres

Pao-Chu Wu et al21 composed and surveyed kept up segment of potassium chloride definitions.

Eudragit RS and/or RL stacked with potassium chloride microspheres were dealt with by

dissolvable dispersal framework. The effect of administered section of Eudragit microspheres

was reviewed by in vitro isolating test and in vivo oral osmosis study, and results were risen up

out of business thing (Slow-K). The results showed that Eudragit microspheres stacked with

potassium chloride can be effortlessly composed and admirable results got considering size

dispersal and conditions of microspheres by joining aluminum stearate. The embodiment limit

and stacking reason for constrainment talked reality 84–90% and 27%, individualy.

2.2 Review of work done of Glipizide

Patel J.K. et al22 engineered and intentionally surveyed in vitro and in vivo shows of

mucoadhesive microspheres of glipizide. Glipizide microspheres containing chitosan were

composed by critical emulsification stage segment system using glutaraldehyde as cross-

accomplice managers. Microspheres were discrete, round, and free spilling. The microspheres

showed incomprehensible mucoadhesive property in vitro wash-off test other than showed high

rate prescription trap capacity. The game plan release was correspondingly kept up for more than

12 hours. The polymer-to-game plan degree had more crucial effect on subordinate variables. In

vivo testing of mucoadhesive microspheres to pale cleaned individual Wistar rats indicated

isolating hypoglycemic effect of glipizide.

Curatolo et al.23 built up secluded framework for utilization in that embodying non-constant

compressible component and connected repository implies for getting and holding medication

containing orally administrable controlled discharge gadget and which in extended structure

opposes gastric travel. Controlled discharge tablets containing antidiabetic medication glipizide

were embedded into repositories of radiopaque. These gadgets were dosed to three fasted beagle

mutts. On account of dosing without GI maintenance gadget, normal Tmax (time at which top

plasma focus was watched) was 2.7 hours and normal AUC (region under plasma fixation versus

time bend) was 35 microgm-hr/ml. On account of dosing with GI maintenance gadget, more or

less consistent glipizide plasma level was watched which stretched out from 3 hours to 12 hours

post-measurement, and normal AUC of 64 microgm-hr/ml was watched. Simultaneous x-beam

estimations showed that glipizide-discharging GI maintenance gadgets were situated in stomach

for no less than 8 hours.

Chowdary KPR et al 24 created, described, and assessed mucoadhesive small scale cases of

glipizide utilizing different mucoadhesive polymers for delayed gastrointestinal retention.

Bhagwat et al 25 made novel strong matrixed controlled discharge, oral estimation structure

where dose structure contains therapeutically suitable measure of sulfonylurea or salt or

reinforcement thereof in framework. Further, utilization of fluid alkalizing medium administers

generously finish bioavailability of remedy from cross area of tablet. Within tablets might then

again be secured with covering material in degree of 2% to 10% with enteric material or with

water insoluble material like ethyl cellulose.

Garcia J. et al 26 endeavored to convey glipizide from circles and compacts containing common

polymer Carrageenan (Gelcarin, GP 812) and arranged by extruder/marumerizer procedure. A

second target was to assess mucoadhesive quality of bioadhesive circles onto bodily fluid film of

rabbit. The impacts of polymer, medication level, and kind of spheronizing material were

assessed. All circle details were compacted into tablets. Results show medication discharge from

circles and compacts diminished as level of Carrageenan was expanded. However as level of

medication was expanded medication discharge additionally expanded. Created bioadhesive

circles and tablets build dissolvability of glipizide which may expand its bioavailability

furthermore expanded adherence of bioadhesive frameworks to mucous layer so that once day by

day measurements can be managed.

Chowdary K.P.R. et. al.27 arranged Ethyl cellulose microspheres of glipizide by modernly

achievable emulsion-dissolvable dissipation strategy and microspheres were explored. The

microspheres are circular, discrete and free-streaming. Exemplification effectiveness was in

scope of 81-91%. Glipizide discharge from microspheres was moderate and dispersion controlled

and reached out more than time of 10 d and relied on upon core:coat proportion, divider density

and size of microspheres. Great straight connections were seen between percent coat, divider

density and discharge rate of microspheres. In in vivo, microspheres created supported

hypoglycemic impact more than 6 d in ordinary rabbits. These microspheres were discovered

suitable for parenteral controlled discharge.

Jamzad S. et al 28 added to another solid cross segment structure to completely go on glipizide,

Biopharmaceutics Classification System (BCS) Class II quiet in zero requesting way more than

expanded time period. Two systems were poor down utilizing arrangement as bit of

inconspicuous components that contain swellable hydroxypropylmethylcellulose (HPMC) or

erodible polyethylene oxide (PEO). The structures were arranged by dry blending picked degrees

of polymers and fixings using direct weight framework. Disintegrating was assessed using

changed USP contraption II. Glucotrol XL push-pull osmotic pump (PPOP) was used as

reference. Straight and reproducible release like that of Glucotrol XL was refined for streamlined

systems (f2 > 50) free of hydrodynamic conditions.

Kuczynski et al29 revealed advancement containing antidiabetic solution glipizide for figuring

out how to patient requiring glipizide treatment. The pressing need exists in like manner for oral

estimations shape that can pass on glipizide at controlled rate in impressively reliable

measurements for every unit time for its valuable remedial effects, and remain altogether free of

changing environment of gastrointestinal tract. It will be recognized further by those skilled in

allocating workmanship, that if such novel and remarkable dosage structure is made open that

can coordinate glipizide in rate-controlled estimation after sooner or later, and all while give

blood-glucose cutting down treatment, measurements structure would identify with progress and

beneficial responsibility to therapeutic craftsmanship

Garg S. et al30developed amplified discharge details of glipizide. Procedures of warm and

isothermal anxiety testing (IST) were utilized to survey similarity of glipizide with chose

excipients. At first, differential checking calorimeter (DSC) was utilized to assess similarity. IR

range of drug–excipient blend was likewise contrasted and that of immaculate medication and

excipient. Similarity of excipients characterized in model recipe was tried utilizing IST. Taking

into account DSC comes about alone, magnesium stearate, meglumine, TRIS cradle, and lactose,

were found to show collaboration with glipizide. Generally speaking, similarity of excipients

with glipizide was effectively assessed utilizing mix of warm and IST techniques and details

created utilizing perfect excipients was discovered to be steable.

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