1. INTRODUCTION
Drug delivery systems are used for maximizing therapeutic index of the drug and also for reduction in the side effects. Oral route remains the prefer route for the administration of therapeutic agents because low cost of therapy and ease of administration leads to higher level of patient compliance. Approximately 50% of the drug delivery systems available in the market are oral drug delivery system [1]. The oral route is considered as the most promising route of the drug delivery and effective oral drug delivery may depend upon many factors such as gastric emptying process, gastrointestinal transit time of the dosage form, drug release from the dosage form and site of absorption of drug.
The high level of patient compliance has been observed in taking oral dosage forms is due to the ease of administration and handling of these forms. Although a lot of advancements have been seen in oral controlled drug delivery system in the last few decades, this system has been of limited success in case of drugs with a poor absorption window throughout the GIT (Gastro Intestinal Tract). To modify the GI transit time is one of the main challenge in the development of oral controlled drug delivery system.
Gastric emptying of pharmaceuticals is highly variable and dependent on the dosage form and the fed/fasted state of the stomach. Normal gastric residence time usually ranges between 5 minutes to 2 hours. In the fasted state the electrical activity in the stomach – the interdigestivemyoelectrical cycle governs the activity and the transit of dosage forms.
It is characterized by four phases [2]:
Phase I- Period of no contraction(30-60 minutes)
Phase II-Period of intermittent contractions (20-40 minutes)
Phase III-Period of regular contractions at the maximal frequency also known as housekeeper
Wave(10-20 minutes)Phase IV-Period of transition between Phase III and Phase I (0-5 minutes)
Gastroretentive systems can remain in the gastric region for several hours and hence significantly prolong the gastric residence time of drugs. Prolonged gastric retention improves bioavailability, reduces drug waste and improves solubility for drugs that are less soluble in a high pH environment. It has applications also for local drug delivery to the stomach and proximal small intestine. Gastro retention helps to provide better availability of new products with new therapeutic possibilities and substantial benefits for patients. Controlled release drug delivery systems that retain in the stomach for a long time have many advantages over sustained release formulations. Such retention systems(i.e. GRDDS) are important for the drugs that are degraded in intestine or for drugs like antacids or certain enzymes that should act locally in thestomach.
Gastric retention may increase solubility for the drugs which are poorly soluble in intestine due to alkaline pH before they are emptied, resulting in improved bioavailability. These systems are also advantages in improving GIT absorption of a drug with narrow absorption windows as well as for controlling release of those drugs which are having site specific absorption limitations. These systems are useful in case of those drugs which are best absorbed in stomach for eg. Albuterol [3]. From the formulation and technological point of view, floating drug delivery system (FDDS) is considerably easy and logical approach in development of GRDFs.
Techniques of GRDDS [4]
FLOATING DRUG DELIVERY SYTEMS-
Floating systems, first described by Davis in 1968, have bulk density lower than that of the gastric fluid and thus remain buoyant in stomach for a prolong period [2]. Swelling delivery systems are capable of swelling to a size that prevents their passage through the pylorus. Upon coming in contact with gastric fluid, the polymer imbibes water and swells; as a result the dosage form is retained in the stomach for a longer period of time [5-6].
Various approaches have been worked out to improve the retention of oral dosage form in the stomach as Floating systems, Swelling or Expanding systems, Bioadhesive systems and High density systems. Floating systems are low density systems that have sufficient buoyancy to float over the gastric contents and remain in the stomach for a prolonged period. While the system floats over the gastric contents, the drug is released slowly at the desired rate, which results in increased gastro-retention time and reduces fluctuation in plasma drug concentration. After release of drug, the residual system is emptied from the stomach. This results in an increased GRT and a better control of the fluctuations in plasma drug concentration [16].
DEFINITION:
Floating Drug Delivery Systems are the drug delivery systems which prolongs the retention of the dosage form in the GIT and aid in enhancing the absorption.
FDDS is also considered as “Hydrodynamically Balanced Systems (HBS).”
These systems are best suited for drugs with having a better solubility in acidic environment.
Also for the drugs having specific site of absorption in the upper part of small intestine.
To remain in the stomach for a prolonged period of time the dosage form have a bulk density<1.
It should stay in the stomach, maintain its structural integrity, and release drug constantly from the dosage form.ADVANTAGES OF FLOATING DRUG DELIVERY SYSTEMS
Enhanced bioavailability-The bioavailability of some drugs (e.g. riboflavin and levodopa) CR-GRDF is significantly enhanced in comparison to administration of non-GRDF CR polymeric formulations [7]. Enhanced first-pass biotransformation-When the drug is presented to the metabolic enzymes (cytochrome P-450, in particular CYP-3A4) in a sustained manner, the presystemic metabolism of the tested compound may be considerably increased rather than by a bolus input [8]. Sustained drug delivery/reduced frequency of dosing-The drugs having short biological half life, a sustained and slow input from FDDS may result in a flip-flop pharmacokinetics and it reduces the dose frequency. This feature is associated with improved patient compliance and thus improves the therapy [8]. Targeted therapy for local ailments in the upper GIT-The prolonged and sustained administration of the drug from FDDS to the stomach may be useful for local therapy in the stomach. Reduced fluctuations of drug concentration-The fluctuations in plasma drug concentration are minimized, and concentration-dependent adverse effects that are associated with peak concentration can be prevented. This feature is of special importance for drugs with a narrow therapeutic index [9]. Improved Receptor activation selectivity – FDDS reduces the drug concentration fluctuation that makes it possible to obtain certain selectivity in the elicited pharmacological effect of drugs that activate different types of receptors at different concentrations [8]. Reduced counter-activity of the body-Slow release of the drug into the body minimizes the counter activity leading to higher drug efficiency. Extended time over critical (effective) concentration-The sustained mode of administration enables extension of the time over a critical concentration and thus enhances the pharmacological effects and improves the clinical outcomes. Minimized adverse activity at the colon-Retention of the drug in GRDF at stomach minimizes the amount of drugs that reaches the colon and hence prevents the degradation of drug that degraded in the colon. DISADVANTAGES OF FLOATING DRUG DELIVERY SYSTEMS [1, 10]
These systems require a high level of fluid in the stomach for drug delivery to float and work efficiently. Not suitable for drugs that have solubility or stability problem in GIT. Drugs such as Nifedipine which is well absorbed along the entire GIT and which undergoes first-pass metabolism, may not be desirable. Drugs which are irritant to Gastric mucosa are also not desirable or suitable. The drug substances that are unstable in the acidic environment of the stomach are not suitable candidates to be incorporated in the systems. The dosage form should be administered with a full glass of water (200-250 ml). These systems do not offer significant advantages over the conventional dosage forms for drugs, which are absorbed throughout the gastrointestinal tract. APPLICATIONS OF FLOATING DRUG DELIVERY SYSTEMS
· Site Specific Drug Delivery-Furosemide is primarily absorbed from the stomach followed by the duodenum [11].
· Sustained Drug Delivery-Sustained release floating capsules of Nicardipine HCl are compared with commercially available MICARD capsules.
· As a result, the plasma concentration time curves showed a longer duration for administration (16 hrs) in sustained release floating capsules [12].
· Absorption enhancement-Bioavailability ranges for
Floating dosage forms:42.9%
Commercially available LASIX Tablets:33.4%
Enteric coated LASIX long product:29.5% [11].
· The administration of Diltiazem floating tablets twice a day may be more effective in controlling the BP of hypertensive patients.
· Modapar HBS containing L-DOPA and Benserazide maintains the substantial plasma concentration for Parkinsonian patients.
<!· Cyotech-containing Misoprostol, a synthetic PG-EL analogue, for prevention of NSAID induced gastric ulcer.
· 5-Fluorouracil has been successfully evaluated in patients with stomach neoplasm.
· Floating microspheres of Indomethacin are quiet beneficial for Rheumatic patients.
· Drugsthat have narrow absorption window in GIT.E.g.:L-DOPA, P-amino benzoic acid, Furosemide, Riboflavin.
· Drugs those are locally active in the stomach. e.g.: Misoprostol, Antacids.
Drugs those are unstable in the intestinal or colonic environment. e.g.: Captopril, Ranitidine HCl, Metronidazole.
· Drugs that disturb normal colonic microbes. e.g.: Antibiotics used for the eradication of H.pylori, such as Tetracycline, Clarithromycin, Amoxicillin.
· Drugs that exhibit low solubility at high pH values. e.g.: Diazepam, Chlordiazepoxide, Verapamil.
· Developing HBS dosage form for Tacrine provides a better delivery system and reduces its GI side effects in Alzheimer’s patients.
· Treatment of gastric and duodenal ulcers.
· Floating microspheres can be used as carriers for drugs with absorption windows.
Eg.: Antiviral, antifungal, antibiotic agents (sulfonamides, quinolones, penicillins, cephalosporins, aminoglycosides, tetracyclines).TYPES OF FLOATING DRUG DELIVERY SYSTEMS
EFFERVESCENT
A. GAS-GENERATING SYSTEMS:
§ It includes the use of
I. Swellable polymers like methocel, polysaccharides (chitosan),
II. Effervescent compounds(NaHCO3, citric acid, tartaric acid) [13]., present in the formulation to produce Carbon-di-oxide such that it reduces the density of the system and makes the dosage form to float on gastric fluid.
§ ALTERNATIVE PROCESS-Incorporation of matrix containing portion of liquid which produce gas that evaporates at body temperature.
§ The effervescent systems further classified into two types:
a) Gas generating systems,
b) Volatile liquid/vaccum containing systems.
a) Gas generating systems:-These systems includes
i. Tablets,
ii. Floating Capsules,
iii. Multiple Unit Type of Floating Pills,
iv. Floating system with Ion Exchange Resin.
i. TABLETS:[14,15]
Þ The low solubility of the drug could be enhanced by using the Kneading method, preparing a solid dispersion with Beta-Cyclodextrin mixed in a 1:1 ratio.
Þ One layer contains the polymers HPMC K4M, HPMC K100M and CMC (for the control of drug delivery) and the drug.
Þ The second layer contains the effervescent mixture of sodium bicarbonate and citric acid.
Þ A floating dosage unit is useful for drugs acting locally in the proximal gastro intestinal tract.
Þ These systems are also useful for drugs that are poorly soluble / unstable in intestinal fluids.
Þ The floating properties of these systems helps to retain these systems in the stomach for a long time.
Þ Various attempts have been made to develop floating systems which float on the gastric contents & release drug molecules for the desired time period.
Þ After the release of a drug, the remnants of the system are emptied from the stomach.
Þ As a floating tablet, HBS is representative. This system is based on the principle that an object of less specific gravity than the gastric fluid will float on the gastric fluid in the stomach for a long period.
Þ Consequently, gastro intestinal residence time will increase. This system is applicable to the drugs that suffer degradation in the intestine, have a higher pH than the stomach, are poorly absorbed from the lower part of the small intestine.
Þ Diazepam, Captopril, Morphine are suitable drugs for this system. These drugs are mixed with gel forming hydrocolloids such as HPMC, fillers of low density in a tablet.
Þ Therefore, the hydrocolloids also retain drug molecules inside the tablet by decreasing the diffusion rate of drug molecules in the gel matrix.
ii. FLOATING CAPSULES:[17,18,19]
Þ Floating capsules are prepared by filling with a mixture of sodium alginate and sodium bicarbonate.
Þ The systems were shown to float during in vitro tests as a result of the generation of CO2 that was trapped in the hydrating gel network on exposure to an acidic environment
Þ A billeted floating capsule was developed for misoprostol. There were two layers in a capsule: a release layer & a floating layer.
Þ The floating layer consisted of Methocel K4M, Lactose, Aerosil 200, magnesium stearate.
Þ The release layer consisted of various combinations of Methocel K4M, K100, drug, HPMC, Pharmacoat 606 & 603.
Þ Large quantities of high-viscosity polymers were incorporated to form a strong viscous layer. This helped in maintaining the integrity of the floating layer for a long time.
Þ The drug release layer consisted of a gelling agent. This helped to avoid disintegration and prevented delivery of large particles containing drug into the intestine, thus reducing side effects.
Þ HALO delivery capsules consists of a biphasic rapid and sustained release formulation contained a lipophilic drug such as propranolol dissolved in oleic acid. Initial rapid release of a drug-oleic acid solution is followed by the subsequent sustained release of those components from a solid erodible matrix containing a Gelucire of low HLB and melting point above 37 c.
Þ A novel in vitro dissolution test method for a floating dosage form with biphasic releasing characteristics was proposed.
iii. MULTIPLE UNIT TYPE OF FLOATING PILLS:[20]
Þ The system consists of sustained release pills as ‘seeds’ surrounded by double layers.
Þ The inner layer consists of effervescent agents while the outer layer is of swellable membrane layer.
Þ When the system is immersed in dissolution medium at body temperature, it sinks at once and then forms swollen pills like balloons, which float as they have lower density.
Þ This lower density is due to generation and entrapment of CO2 within the system.
iV. FLOATING SYSTEM WITH ION-EXCHANGE RESINS:[21]
Þ A floating system using ion exchange resin that was loaded with bicarbonate by mixing the beads with 1M sodium bicarbonate solution.
Þ The loaded beads were then surrounded by semi-permeable membrane to avoid sudden loss of CO2.
Þ Upon coming in contact with gastric contents an exchange of chloride and bicarbonate ions took place that resulted in CO2 generation thereby carrying beads toward the top of gastric contents and producing a floating layer of resin beads.
A. VOLATILE LIQUID/VACCUM CONTAINING SYSTEM:
It includes
i. Intra gastric floating gastro intestinal drug delivery system,
ii. Inflatable gastrointestinal drug delivery system,
iii. Intra gastric osmotically controlled drug delivery system.
I. INTRAGASTRIC FLOATING GASTROINTESTINAL DRUG DELIVERY SYSTEM:-[22]
Þ These systems can be made to float in the stomach because of flotation chamber, which may be a vaccum/ filled with air/harmless gas, while drug reservoir is encapsulated inside a microporous compartment.
II. INFLATABLE GASTROINTESTINAL DRUG DELIVERY SYSTEM:-[23]
Þ In these systems, an inflatable chamber is incorporated, which contains liquid ether that gasifies at body temperature to cause the chamber to inflate in the stomach.
Þ These systems are fabricated by loading the inflatable chamber with a drug reservoir, which can be a drug impregnated polymeric matrix, encapsulated in a gelatin capsule.
Þ After oral administration, the capsule dissolves to release the drug reservoir together with the inflatable chamber.
Þ The inflatable chamber automatically inflates and retains the drug reservoir compartment in the stomach.
Þ The drug continuously released from the reservoir into the gastric fluid.
iii. INTRAGASTRIC OSMOTICALLY CONTROLLED DRUG DELIVERY SYSTEM:-
Þ It is comprised of an osmotic pressure controlled drug delivery device and an inflatable floating support in a biodegradable capsule.
Þ In the stomach, the capsule quickly disintegrates to release the intragastricosmotically controlled drug delivery system.
Þ The inflatable support inside forms a deformable hollow polymeric bag that contains a liquid that gasifies at a body temperature to inflate the bag.
Þ The osmotic pressure controlled drug delivery system consists of two compartments; drug reservoir compartment and an osmotically active compartment.
Þ The drug reservoir compartment is enclosed by a pressure responsive collapsible bag, which is impermeable to vapour and liquid & has a drug delivery orifice.
Þ The osmotically active compartment contains an osmotically active salt and is enclosed within a semipermeable membrane.
Þ In stomach, the water in GI fluid is continuously absorbed through the semipermeable membrane into osmotically active compartment to dissolve the osmotically active salt.
Þ The osmotic pressure thus created acts on the collapsible bag in turn forces the drug reservoir compartment to reduce its volume and activate drug release through the delivery orifice.
Þ The floating support is also made to contain a bioerodible plug that erodes after a predetermined time to deflate the support. The deflated drug delivery system is then emptied from the stomach.
2.NON-EFFERVESCENT SYSTEMS:
In this type of system, after swallowing, the dosage form swells unrestrained through imbibitions of gastric fluid to an extent that it prevents their exit from the stomach.
Formulation Method- Mixing of the drug with a gel, which swells when comes in contact with gastric fluid and maintains a relative integrity of shape and a bulk density of <1 within the outer gelatinous barrier [24]. The air trapped by the swollen polymer provides buoyancy to these dosage forms.
Excipients: HPMC, Poly acrylate polymers, poly vinyl acetate, carbopol, agar, sodiumalginate, calcium chloride, poly ethylene oxide and poly carbonates.
i. COLLOIDAL GEL BARRIER SYSTEM:
Sheth and Tossounian first designated this ‘hydrodynamically balanced system [25].’
It contains drug with gel forming hydrocolloids meant to remain buoyant on the stomach content. This prolongs GRT and maximizes the amount of drug at its absorption sites in the solution form for ready absorption.
On coming in contact with gastric fluid, the hydrocolloid in the system hydrates and forms a colloidal gel barrier around its surface and also helps in sustain releasing of drug.
Excipients:- HPMC, HEC, Polysaccharides-highly soluble cellulose type hydrocolloids, Poly carbophil, Poly acrylate, Polystyrene-Matrix forming polymers.
ii. MICRO POROUS COMPARTMENT SYSTEM:
It is based on the encapsulation of a drug reservoir inside a micro porous compartment with pores along its top & bottom walls [26].
The peripheral walls of the drug reservoir compartment are completely sealed. This sealing prevents any direct contact of gastric surface with the undissolved drug.
The floatation chamber containing entrapped air allows the delivery system to float over gastric content, in the stomach.
*Gastric fluid enters through the aperture, dissolves the stric fluid to an extent such that it prevents their exit from the drug and carries the dissolved drug for continuous transport across the intestine for absorption.
iii. ALGINATE BEADS:Multi unit floating dosage forms were developed from freeze-dried calcium alginate [27].METHOD OF PREPARATION OF FLOATING DRUG DELIVERY SYSTEMS(ALGINATE BEADS)
iv. HOLLOW MICROSPHERES/MICRO BALLOONS:[28]
<!--[if !supportLists]-->v <!--[endif]-->Method of preparation-Novel emulsion-solvent diffusion method.
<!--[if !supportLists]-->v <!--[endif]-->Excipients-Ethanol, dichloro methane, enteric acrylic polymer, poly vinyl alcohol.
The gas phase is generated in the dispersed polymer droplet by the evaporation of dichloromethane formed in the internal cavity of microsphere of the polymer and drug.
The micro balloons float continuously over the surface of acidic dissolution media containing surfactant for more than 12 hours.
v. SINGLE LAYER FLOATING TABLETS: [29]
These are prepared by intimate mixing of drug with gel-forming hydrocolloid, which swells in contact with gastric fluid and maintains bulk density of <1.
Also prepared by intimate mixing of drug with low density enteric materials such as CAP, HPMC.
vi. BI-LAYER FLOATING TABLETS:[30]
A bi-layer tablet consists of two layers: One immediate release layer which releases initial dose from system. The another sustained release layer absorbs gastric fluid, forming an impermeable colloidal gel barrier on its surface.
It maintains a bulk density of<1 and thereby it remains buoyant in the stomach.MECHANISM OF FLOATING SYSTEM
MECHANISM OF FLOATING SYSTEMS[31]
However, besides a minimal gastric content needed to allow the proper achievement of the buoyancy [32,33] retention principle, a minimal level of floating force (F) is also required to keep the dosage form reliably buoyant on the surface of the meal.
To measure the floating force kinetics, a novel apparatus for determination of resultant weight has been reported.
The apparatus operates by measuring continuously the force equivalent to ‘F’ that is required to maintain the submerged object.
The object floats better if F is on the higher positive side.
This apparatus helps in optimizing FDDS with respect to stability and durability of floating forces produced in order to prevent the drawbacks of unforeseeable intra gastric buoyancy capability variations.
F = F buoyancy – F gravity
= ( Df – Ds ) gv
Where
F = total vertical force
Df=fluid density
Ds=object density
v=volume
g=acceleration due to gravity.
METHODS OF PREPARATION
1. Using gel forming hydrocolloids such as hydrophilic gums, gelatin, alginates, cellulose derivatives, etc.
2. Using low density enteric materials such as methacrylic polymer, cellulose acetate phthalate(CAP).
3. By reducing particle size and filling it in a capsule.
4. By forming co2 gas and subsequent entrapment of the gel network.
5. By preparing hollow microballoons of drug using acrylic polymer and filled in capsules.
6. By incorporation of inflatable chamber which contained in a liquid.
e.g.: Solvent that gasifies at body temperature to cause the chambers to inflate in the stomach.
7. A novel emulsion solvent diffusion method was used to prepare hollow microspheres loaded with the drug in their outer polymer shelf.
8. Simple blending of drug and selected polymers along with excipients- in case of floating capsules.
9.Direct compression method for effervescent approach- in case of floating tabletsTYPES OF FLOATING DOSAGE FORMS:
S.NO | DOSAGE FORMS | DRUGS |
1. | FLOATING MICROSPHERES | Aspirin, Griseofulvin, P- nitro aniline [34], Ibuprofen,Terfinadine[35], Tranilast[36]. |
2. | FLOATING GRANULES | Diclofenac sodium[37], Indomethacin[38] and Prednisolone[39]. |
3. | FLIMS | Cinnarizine[40] |
4. | FLOATING CAPSULES | ChlordiazepoxideHCl[41], Diazepam[42], Furosemide[11],Misoprostol[43], L-DOPA & Benserazide[44], Ursodeoxycholic acid[45], pepstatin. |
5. | FLOATING TABLETS | Furosemide[30], Ciprofloxacin[46], Verapamil HCl[47]. |
6. | POWDERS | Several basic drugs[48]. |
COMMERCIAL FLOATING FORMULATIONS:[4,49]
S.NO | NAME | TYPE AND DRUG | REMARKS |
1. | Madopar HBS (propel HBS) | Floating capsule, Levodopa &Benserazide. | Floating CR Capsules. |
2. | Valrelease | Floating capsule, Diazepam. | Floating capsules. |
3. | Topalkan | Floating Antacid, Aluminiumand magnesium mixture. | Effervescent floating liquid alginate preparation. |
4. | Amalgate float coat | Floating antacid Floating gel. | Floating dosage form. |
5. | Conviron | Ferrous sulphate | Colloidal gel forming form. |
6. | Cifran OD | Ciprofloxacine(1 gm ). | Gas generating floating form. |
7. | Cyotech | Misoprostol(100mg/200mg). | Bilayer floating capsule. |
8. | Liquid. Gaviscone | Mixture of alginate. | Suppress gastro-oesophageal reflux and alleviate the heart burn. |
FORMULATION OF FLOATING DOSAGE FORMS:
The following types of the ingredients can be incorporated into Floating Drug Delivery Systems.
a. Hydro colloids
b. Inert Fatty materials
c. Release Rate Accelerants
d. Release Rate Retardants
e. Buoyancy Increasing Agents
f. Miscellaneous
a. HYDRO COLLOIDS:
Suitable hydro colloids are synthetics, anionic or non-ionic like hydrophilic gums, modified cellulose derivatives.
e.g.: Acacia, pectin, agar, alginates, gelatin, casein, bentonite, veegum, methyl cellulose,
hydroxy propyl cellulose, hydroxyl ethyl cellulose, and sodium carboxy methyl-
cellulose are used.
b. INERT FATTY MATERIALS:
Edible, pharmaceutical inert fatty material, having a specific gravity less than 1 can be added to the formulation inorder to decrease the hydrophilic property of formulation and hence increases the buoyancy.
e.g.: Purified grades of bees wax, fatty acids, long chain alcohols, glycerides, mineral oils.
c. RELEASE RATE ACCELERANTS:
The release rate of the medicament from the formulation can be modified by using excipients like lactose and or mannitol (5-60%w). E.g.: Lactose, mannitol.
e.RELEASE RATE RETARDANTS:
These are used to decrease the solubility and hence retards the rate of release of medicaments.
e.g.: Di calcium phosphate, talc, magnesium stearate.
5. BUOYANCY INCREASING AGENTS:
Materials like ethyl cellulose, which has bulk density less than 1, can be used for enhancing the buoyancy of the formulation. It may be used upto 80% by weight.
6. MISCELLANEOUS:
Pharmaceutically acceptable adjuvants like preservatives, stabilizers, lubricants can be used in the dosage forms as per the requirements.
They do not adversely affect the hydrodynamic balance of the systems.
EVALUATION PARAMETERS OF FLOATING DRUG DELIVERY SYSTEM:
Different studies reported in the literature indicate that pharmaceutical dosage forms exhibiting gastric residence in vitro floating behavior show prolonged residence in vivo. However, it has to be pointed out that good in vitro floating behavior alone is not sufficient proof for efficient gastric retentionin vivo. The effects of the simultaneous presence of food and of the complex motility of the stomach are difficult to estimate. Obviously, only in vivo studies can provide definite proof that prolonged gastric residence is obtained.
1.Measurement of buoyancy capabilities of the FDDS
The floating behavior was evaluated with resultant weight measurements. The experiment was carried out in two different media like deionised water and simulated meal, in order to monitor possible difference. The results showed that higher molecular weight polymers with slower rate of hydration had enhanced floating behavior and which was more in simulated meal medium compared to deionised water [50].
2.Floating time
The test for floating time is usually performed in simulated gastric fluid or 0.1 mole.lit-HCl maintained at 37 c , by using USP dissolution apparatus containing 900ml of 0.1 molar HCl as the dissolution medium. The time taken by the dosage form to float is termed as floating lag time and the time for which the dosage form is termed as the floating or floatation time [51].
3.Drug release
Dissolution tests are performed using the dissolution apparatus. Samples are withdrawn periodically from the dissolution medium with replacement and then analyzed for their drug content after an appropriate dilution.
4.Content uniformity, Hardness, Friability (Tablets)
These tests are performed as per described in specified monographs.
5.Drug loading, drug entrapment efficiency, particle size analysis, surface characterization(for floating microspheres and beads)
Drug loading is assessed by crushing accurately weighed sample of beads or microspheres in a mortar and added to the appropriate dissolution medium which is then centrifuged, filtered and analyzed by various analytical methods like spectrophotometry. The percentage drug loading is calculated by dividing the amount of drug in the sample by the weight of total beads or microspheres. The particle size and the size distribution of beads or microspheres is determined in the dry state using the optical microscopy method. The external and cross-sectional morphology (surface characterization) is done by scanning electron microsphere(SEM) [52].
6.Resultant weight
The in vitro measuring apparatus has been conceived to determine the real floating capabilities of buoyant dosage forms as a function of time. It operates by force equivalent to the force F required to keep the object totally submerged in the fluid. This force determines the resultant weight of the object when immersed and may be used to quantify its floating or non floating capabilities. The magnitude and direction of the force and the resultant weight corresponds to the Victoria sum of buoyancy (F buoy) and gravity (F grav) forces acting on the objects as shown in the equation
F=F buoy – F grav
F=dfgv-dsgv=(df-ds)gv
F=(df-M/V)gv
In which the F is total vertical force (resultant weight of the object), g is the acceleration due to gravity, df is the fluid density, ds is the object density, M is the object mass and V is the volume of the object [53].
7.X-Ray/Gamma Scintigraphy
X-Ray/ Gamma Scintigraphyis a very popularily used evaluation parameter for floating dosage form these days [54]. It helps to locate dosage form the GIT and by which one can predict and correlate the gastric emptying time and the passage of dosage form in the GIT. Here the inclusion of a radio-opaque material into a solid dosage form enables it to be visualizedby X-rays. Similarly, the inclusion of a gamma-emitting radionucleide in a formulation allows indirect external observation using a gamma-camera or scintiscanner.
8.Pharmacokinetic studies
Pharmacokinetic studies are the integral part of the in vivo studies. Sawicki et al studied the pharmacokinetics of Verapamil, from the floating pellets containing drug, filled into a capsule, and compared with the conventional Verapamil tablets of similar dose (40 mg) [55]. The t -max and AUC (0-infinity) values (37.5 h and 364.65 ng.ml-1hr respectively) for floating pellets were comparatively higher than those obtained for the conventional Verapamil tablets. (t max value 1.21hr, and AUC value 224.22 ng.ml-h=1hr). No much difference was found between the C -max values of both the formulations, suggesting the improved bio availability of the floating pellets compared to the conventional tablets. The microspheres showed about 1.4 times more bio availability, and the elimination half-life was increased by about three times than the free drug.
9. Specific Gravity
S.Sangekar et al purposed Specific Gravity of the floating system can be determined by the displacement method using benzene as a displacing medium [10].
CONCLUSION:
Drug absorption in the gastro intestinal tract is a highly variable procedure and prolonging gastric retention of the dosage form extends the time for drug absorption. FDDS promises to be a potential approach for gastric retention.
FUTURE POTENTIAL
Among the recently used clinical drugs several narrow absorption window drugs may benefit from compounding into a FDDS. Replacing parenteral administration of drugs to oral pharmacotheraphy would substantially improve treatment. It may be believed that it can be possible with FDDS. Drugs that have poor bio-availability because of their limited absorption to the upper gastro intestinal tract can be delivered efficiently into FDDS. Thereby maximizing their absorption and improving their absolute bioavailability. The floating concept can also be utilized in the development of various anti-reflux formulations. Developing a controlled release system for the drugs, which are potential to treat the Parkinson’s disease, is also an important area of consideration. Combination therapy to treatH.pyori infection in a single FDDS needs to be developed. The study of the effect of various geometric shapes in a more excessive manner than previous studies on gastro retentivity needs to be developed. The investigations can be concentrated on the concept of design of novel polymers according to clinical and pharmaceutical need.
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