Floating Drug Delivery Systems: An updated Review

 

Shaik. Mohammad Farooq, Syed. Sunaina, M. Durga Srinivas Rao, P. Venkatesh, D. Hepcykalarani, R. Preama

Jagan’s Institute of Pharmaceutical Sciences, Jangalakandriga (v) - 524 326, Muthukur (M), Nellore (Dist.), A.P., India.

*Corresponding Author E-mail: skfarooqpharma@gmail.com

 

ABSTRACT:

Recent technological and scientific research has been devoted to develop special focus on principal mechanism of floating drug delivery systems (FDDS) to over Come physiological and formulation variables affecting gastric Residence times and unpredictable gastric emptying times approaches to design single-unit and multiple-unit floating systems. The present review explains briefly about Floating drug delivery systems. It also summarizes the in vivo and in vitro studies to develop performance and applications of floating systems. This system are more useful to solve various problems that raised during the development of pharmaceutical dosage forms.

 

KEYWORDS: Floating drug delivery systems (FDDS), single units, multiple units, applications.

 

 

 

INTRODUCTION:

Gastric emptying of dosage forms is an extremely variable process and ability to prolong and control the emptying time is valuable asset for dosage forms, which reside in the stomach for a longer period of time than conventional dosage forms several difficulties are faced in designing controlled release systems for better absorption and enhanced bioavailability.1-3 to confine the dosage form in the desired area of gastrointestinal tract .several approaches are  currently utilized in th prolongation of gastric residence times, including swelling and expanding systems and floating drug delivery systems, shape systems and other delayed gastric emptying device .

 

The controlled gastric retention of solid dosage forms may be achieved by the mechanism of mucoadhesion, flotation, sedimentation, expansion, modified shape systems or by simultaneous administration of pharmacological agents that delay gastric emptying based on this approaches classification of FDDS has been described in detail.4-6 In vivo / in vitro evaluation of FDDS has been discussed by scientists to assess the efficiency and application of such systems .several recent examples have been reported showing the efficiency of such systems for drugs with bioavailability problems.7-9 The successful development of oral controlled drug delivery systems requires an understanding of three aspects of the system namely:

·       Physiochemical characteristics of the drug

·       Anatomy and physiology of GIT

·       Characteristics of dosage forms

 

Which reside in the stomach for longer period of time than conventional dosage form. to overcome this physiological problem, several drug delivery systems with prolonged gastric retention time have been investigated. Attempts are being made to develop a controlled drug delivery system that can provide therapeutically effective plasma drug concentration levels for longer durations, there by minimizing fluctuations in plasma drug concentration at steady state by reproducible manner that are less soluble in high pH environment.10-12

 

Basic gastrointestinal tract physiology:

Anatomically the stomach is divided into 3 regions fundus, body and antrum (pylorus). The main function of the stomach is to process and transport food. The roximal art made of fundus and body acts as a reservoir for undigested material, whereas the ntrum is the main site for mixing motions and acts as a pump for gastric emptying by propelling actions. gastric emptying occurs fasting as well as fed states. The pattern of motility is however distinct in the 2 states. During fasting state an interdigestive series of electrical events take place , which cycle both throug stomach and intestine every 2 to 3 h. This is called the interdigestive myloelectric cycle or migrating myloelectric cycle (MMC), which is further divided into following 4 phases as described by Wilson and Washington.13-15

 

 

Fig.1. Structure of stomach

 

Phase I (basal phase):

Last from 30 to 60 min with rare concentration.

 

Phase II (preburst phase):

Lasts for 20 to 40 min with intermittent action potential and contractions. As the phase progresses the  intensity and frequency also gradually increases.

 

Phase III (burst phase):

Lasts for 10 to 20 min. It includes intense and regular contractions for short period. It is due to this wave That all the undigested material is swept out of the stomach down to the small intestine. Also known housekeeper wave.

 

Phase IV:

Lasts for 0 to 5 minutes and occurs between phase III and I of 2 consecutive cycles. contractions changes from fasted to that of fed state. This is also known as digestive motility pattern and comprises contractions as in phase II of fasted state. These contractions result in reducing the size of food particles 9 (to less than 1 mm), which are propelled toward the pylorus in a suspension from. During the fed state onset of MMC is delayed resulting in slowdown of gastric emptying rate.16-18

 

 

Fig.2. Motility pattern in GIT

 

FDDS:

Floating systems or hydro dynamically controlled systems are low-density systems that have sufficient buoyancy to float over the gastric contents and remain buoyant in in the stomach without affecting the gastric emptying rate for a prolonged period of time. While the system is floating on the gastric contents, the drug is released slowly at the desired rate from the system. After release of drug, the residual system is emptied from the stomach. This result is seen an increased GRT and a better control of the fluctuations in plasma drug concentration. However, besides a minimal gastric content needed to allow the proper achievement of the buoyancy 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. Many buoyant systems have been developed based on granules, powders, capsules, tablets, laminated films and hallow microspheres.19

 

Classification of FDDS20:

Single  unit  floating systems:

Non-effervescent systems (hydro dynamically balanced systems)

 

Effervescent  systems (gas-generating systems)

 

Multiple unit floating systems:

Non-effervescent systems (hydro dynamically balanced systems)

Effervescent systems (gas-generating systems)

Hallow microspheres

Raft forming systems

 

Approches to desgin FDDS:

The fallowing approaches have been used for the  design of floating dosage forms of single-multiple-unit systems.

 

 

Fig.3. Intragastric residence positions of floating and non-floating DDS

 

Single-unit dosage forms:

In low-density approach the globular shells apparently having lower density than that of gastric fluid can be used as a carrier for drug for its controlled release. A buoyant dosage form can also be obtained by using a fluid-filled system that floats in the stomach. In coated shells popcorn, poprice and polystyrol have been exploited as drug carriers. Sugar polymeric materials such as methacrylic polymer and cellulose acetate phthalate have been used to undercoat these shells. These are further coated with a drug-polymer mixture.The polymer of choice can be either ethylcellulose or hydroxypropyl cellulose depending on the type of release desired . finally, the product floats on the gastric fluid while releasing the drug gradually over a prolonged duration. Fluid filled floating chamber is a type of dosage forms includes incorporation of gas-filled floatation chamber into an microporous component that houses a drug reservoir. Apertures or openings are present along the top and bottom walls through which the gastrointestinal tract fluid enters to dissolve the drug. The other two walls in contact with the fluid are sealed so that the un-dissolved drug remains therein. The fluid present could be air, under partial vacuum or any other suitable gas, liquid, or  solid having an appropriate specific gravity and an inert behavior. Hydro dynamically balanced systems (HBS) are designed to prolong the stay of the dosage forms in the gastro intestinal tract and aid in enchancing the absorption. such systems are best suited for drugs having a better solubility in acidic environment nd also for the drugs having specific site of absorption in the upper part of the small intestine. To remain in the stomach or prolonged period of time the dosage form must have a bulk density of less than 1. The success of HBS capsule as a better system is best exemplified with chlordiazeopoxide hydrochloride. the drug is a classical example of a solubility problem wherein it exhibits a 4000-fold difference in solubility going from pH 3 to 6 (the solubility of chlordiazeopoxide hydrochloride is 150 mg/mL and is ~0.1mg/mL at neutral pH). HBS of chlordiazeopoxide hydrochloride had comparable blood level time profile as of there 10-mg commercial capsules. HBS can either be formulated as floating tablet or capsule. Many polymers and polymers combinations with wet granulation as a manufacturing technique have been explored to yield floatable tablets. Various type of tablets (bilayered and matrix) have been show to have floatable characteristics. Some of the polymers used hydroxypropyl cellulose, hydroxypropyl methylcellulose, crosspovidone, sodium carboxymethyl cellulose, and ethyl cellulose. Self correcting floatable asymmetric configuration drug delivery system employs a  disproportionate 3-layer matrix technology to control drug release. Single-unit formulations are associated with problems such as sticking together or being obstructed in the gastrointestinal tract, which may have a potential danger of producing irritation.21

 

Non-effervescent systems/HBS:

These are single-unit dosage forms. non-effervescent floating dosage forms use a gel forming or swellable cellulose type of hydrocolloids, polysaccharides, and matrix- forming polymers like  polycarbonate, polyacrylate, polymethacrylate, and polystyrene. The formulation method includes a simple approach of thoroughly mixing the drug and the gel-forming hydrocolloid. After oral administration this dosage form swells in  contact  with gastric fluids and attains a bulk density of < 1. The air entrapped within the swollen matrix imparts buoyancy to the dosage form. The  so formed swollen gel-like structure acts as a reservoir and allows sustained release of drug through the gelatinous mass. Effective drug delivery depends on the balance of drug loading and the effect polymer on its release profile.22

 

 

 Fig.4. Working  principle of  HBS

 

Gas-generating systems:

These are matrix types of systems prepared with the help of  swellable polymers  such  as methylcellulose and chitosan and various effervescent compounds, eg ,sodium bicarbonate, citric acid floatability can also be achieved by generation of gas bubbles. CO2 can be generated in suit by incorporation of carbonates or bicarbonates which react with acid ,either the natural gastric acid or co-formulated as citric or tartaric acid. The optimal stoichiometric ratio of citric acid and sodium bicarbonate for gas generation is reported to be 0.76:1. Gastric floating drug delivery system (GFDDS) offers numerous advantages over other gastric retention systems . these systems have bulk density lower than gastric fluid and thus remain buoyant in the stomach without affecting the gastric emptying rate or a prolonged period of time. While the systems is floating on the gastric contents , the drug is  released slowly at desired rate from the stomach.23

 

 

Fig.5. Gas-generating systems Multiple-unit dosage  forms:

 

The purpose of designing multiple-unit dosage form is to develop a reliable formulation that has all the advantages of single-unit form and also is devoid of any of  the above mentioned disadvantages of single-unit formulations. In pursui of this endeavor many multiple-unit floatable dosage forms have been designed. Microspheres have high loading capacity and many polymers have been used such  as albumin, gelatin, starch, polymethacrylate, polyacrylamine, and polyalkylcyanoacrylate. Spherical polymeric microsponges, also referred to as ‘microballoons, have been prepared. microspheres have a characteristic internal hallow structureand show an excellent in  vitro floatability. In carbon dioxide- generating multiple-unit oral formulations several devices with features that extend, un-fold, or are inflated by CO2 generated  in the devices after administration have been described in the recent patent literature.24

 

Hallow microspheres:

Hallow microspheres loaded with drug in their outer polymer shelf wre prepared by novel emulsion solvent diffusion method. The ethanol/dichloromethane solution of the drug and an enteric acrylic polymer was poured into an agitated solution of poly vinyl  alcohol (PVP) that was thermally controlled as 400oC. The gas phase is generated in the dispersed polymer droplet by the evaporation of dichloromethane formed and internal cavity in the microsphere of the polymer with drug. The microballoon floated continuously over the surface of an acidic dissolution media containing surfactant for more than 12 h.25

 

Raft forming systems:

Raft forming systems have been received much delivery for gastrointestinal infections and disorders. The mechanism involved in the raft formations includes the formation of viscous cohesive gel in contact with gastric fluids, wherein each portion of the liquid swells forming a continuous layer called a raft. This raft floats on gastric fluids because of low bulk density created by the formation of carbon dioxide. Usually, the system contains a gel forming agent and alkaline bicarbonates or carbonates responsible for the formation of CO2 to make the system less dense and float on the gastric fluids an antacid raft forming floating  systems.26

 

Mechanism  of  FDDS:

FDDS have bulk density lesser than gastric fluid, so they remain buoyant in the stomach without affecting the gastric emptying rate for a prolonged period of time. While the systems is floating on the gastric contents, the drug is released slowly at the desired rate from the system. However, besides 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 in the literature. The apparatus operates by measuring continuously the force equivalent to F (as a function of time) that is required to maintain the submerged object. This apparatus helps in optimizing FDDS with respect to stability and durability of floating forces produced in order to prevent the drawbacks of unforeseeable intragastric buoyancy capability variations.27

 

Advantages of FDDS28:

·       Enhanced bioavailability

·       Sustained drug delivery /reduced frequency of dosing

·       Targeted therapy for local aliments in the upper GIT

·       Reduced fluctuations of drug concentration

·       Improved selectivity in receptor activation

·       Reduced counter-activity of the body

·       Extended effective concentration

·       Minimized adverse activity at the colon

 

Disadvantages of FDDS29:

·       The drug substance that are unstable in the acidic environment of the stomach are not suitable candidates to be incorporated in the systems.

·       These systems require a high level of fluid in the stomach for drug delivery to float and work efficiently

·       Gastric retention is influenced by many factors such as gastric motility, pH, and presence of food . these factors are never constant and hence the buoyancy cannot be predicted.

·       Drugs that cause irritation and lesion to gastric mucosa are not suitable to be formulated as FDDS.

 

Approches  to  gastroretenation30:

Several    techniques  are  reported  in  the  literature  to  increase the  gastric  retention  of  drugs.  

 

High  density  systems:

These  systems, which  have  a  density  of  ~3g/cc, are retained  in  the  rugae  of  stomach  and  capable  of  withstanding its  peristaltic  movements. The only major drawback with these  systems is that it is technically difficult   to  manufacture   them  with  a  large  amount  of  drug (> 50%) and achieve  required  density  of  2.4-2.8g/cc.    Diluents  such   as  barium  sulphate   (density = 4.9g/cc), zinc oxide < titanium  oxide <  and   iron  powder   must  be  used  to manufacture  such  high-density   formulation.

 

Swelling  and  expanding   systems:

These   systems  are  also  called  as  “plug  type  systems”, since   they  exhibit  tendency  to  remain    logged  in  the  pyloric  sphincters.  These  polymeric  matrices  remain  in  the  gastric  cavity  for  several  hours   even  in  fed  state  by  selection   of  polymer  with  the    proper  molecular  weight  and  swelling  properties  controlled  and  sustained  drug  release  can  be  achieved.  Upon  coming  in  contact  with  gastric  fluid,  the  polymer  imbibes  water  and swells

 

Mucoadhesive and bioadhesive systems:

Bioadhesive drug delivery systems are used to localize a delivery device within the lumen to enhance the drug absorption in a site-specific manner. This approach involves the use of bioadhesive polymers, which can adhere to the epithelial surface in the stomach. Some of the most promising excipients that have been used commonly in the these systems include polycarbophil, carbopol, lectins, chitosan, CMC and gelatin, etc

 

Floating systems:

Floating systems have a bulk density less than gastric fluids and so remain buoyant in the stomach without affecting the gastric emptying rate for a prolonged period of time. While the systems is floating on the gastric contents, the drug is released slowly at the desired rate from the systems. After release of drug,  the residual system is emptied from the stomach. Floatation of a drug delivery system in the stomach can be achieved by incorporating floating chamber filled with vacuum, air, or inert gas

 

Modified systems:

Systems with non disintegrating geometric shape molded from silastic Elastomers or extruded from polyethylene blends, which extended the GRT depending on size, shape and flexural modules of drug delivery device.

 

Factors affecting gastric retenation31,32:

Density:

GRT is a function of dosage from buoyancy that is dependent on the density

 

Size:

Dosage form units with a diameter of more than 9.5mm are reported to have an increased GRT.

 

Shape of dosage form:

Is one of the factors that affect its gastric residence time. Six shapes (ring, tetrahedron, clover leaf, string, pellet, and disk) were screened in vivo for their gastric retention potential. The tetrahedron (each leg 2cm long) rings (3.6 cm in diameter) exhibited nearly 100% retention at 24 h.

 

Frequency of feed:

The GRT can increase by over 400 min when successive meals are given compared with a single meal due to low frequency of MMC.

 

Age:

Elderly people, especially those over 70yr, have a significantly longer GRT.

 

Evaluation of FDDS:

There are different studies reported in the literature indicate that pharmaceutical dosage exhibiting gastric residence in vitro floating behaviour show prolonged gastric residence in vivo. However, it has to be pointed out that good in vitro floating behaviour alone is not sufficient proof for efficient gastric retention in vivo. These effects of the simultaneous presence are difficult to estimate. Obviously, only in vivo studies can provide definite proof that prolonged gastric residence is obtained.33-36

 

Pre-compression studies:

The blends of FDDS were evaluated for their flow and compression properties.37

 

Angle of Repose (θ):

Was determined by funneling method, the blend was poured through the walls of a funnel, which was fixed at a position such that its lower tip was at a height of exactly 2 cm above hard surface. The blend was poured till the time when the upper tip of the pile surface touched the lower tip of the funnel. The θ is calculated by the equation.

 

θ=tan–1h/r        Eq. No.                                                 (1)

 

Where, θ = angle of repose, h = height of the heap and r = radius of base of heap circle.

 

Bulk density (BD): BD was determined by pouring into a graduated cylinder a weighed amount of blend and measuring its volume.

 

 BD = wt.of blend/ Bulk volume                     Eq. No. (2)

 

Tapped density (TD):

TD was determined by by pouring into a graduated cylinder a weighed amount of blend. The cylinder was permitted to drop at 2-second intervals on a surface below its own weight from the height of 10cm. The tapping continued until no additional volume shift was observed.

 

TD = Wt. of blend / Tapped volume               Eq. No. (3)

 

Compressibility Index (CI): 

By using Carr’s index the compressibility of the blends can be determined.

 

CI = (TD-BD) ×100/TD                                  Eq. No. (4)

 

Hausner’s Ratio (HR):

Is a number that correlates to the flow ability of a powder. It is calculated by the equation.

 

HR =TD/BD                                                    Eq. No. (5)

 

Post-compression studies38-40:

 

Tablet dimensions:

Thickness and diameter were measured using a calibrated vernier caliper. three tablets of each formulation were picked randomly and thickness was measured individually

 

Hardness:

Hardness indicates the ability of a tablet to withstand mechanical shocks while handling . the hardness of the tablet was determined using Monsanto hardness tester. It was expressed in kg/cm2. Three tablets were randomly picked and hardness of the tablet was determined

 

Weight  variation  test:

Ten tablets were selected randomly from each batch And weighed individually to check for weight variation. A little variation was allowed in the weight of tablet by U.S. pharmacopoeia. The following percentage deviation in weight variation was allowed show in table

 

Tablet  density:

Tablet density was an important parameter for floating tablets. The tablets would floats only when its density was lass than that of gastric fluid (1.004g/cc).  the density was determined using following relationship

 

v=r2h                                                                Eq. No. (6) 

 

d=m/v                                                               Eq. No. (7)

 

Where: b = volume of tablet (cc), r = radius of tablet (cm), h = crown thickness of tablet (g/cc) and m = mass of tablet (g)

 

Friability test:

The friability of tablets was  determined by using roche friabilator. It was expressed in percentage (%). Ten tablets were initially weighed (W0) and transferred  into friabilator. The friabilator was operated at 25rpm for 4 minutes or run up to 100 revolutions . the tablets were weighed again (W). The % friability was then calculated by

 

% F=(W0-W)×100/W0                                     Eq. No. (8)

 

In vitro buoyancy studies:

The floating behaviour was evaluated with resultant weight measurements. The experiment was carried out in two different media, de-ionised water in order to monitor possible difference. The apparatus and its mechanism are explained earlier in this article. The results showed that higher molecular weight polymers with slower rate of hydration had enhanced floating behaviour and it was observed more in simulated meal medium compared to deionized water.

 

In vitro dissolution studies:

The test for floating time measurement is usually performed in stimulated gastric fluid or 0.1mol/L HCI maintained at 37oC. it is determined by using USP dissolution apparatus containing 900ml of 0.1mol/L HCL as the dissolution medium 37oC. The time taken by the dosage from to float is termed as floating lag time and the time for which the dosage form floats is termed as the floating or flotation time. A more revelant in-vitro dissolution method proposed to evaluate a FDDS (tablet). A 100mL  glass  beaker was modified by adding a side arm at the bottom of the beaker so that the beaker can hold 70mL of 0.1mol/L HCL dissolution medium and allow collection of samples. A burette was mounted above the beaker to deliver the dissolution medium at a flow rate 2mL/min to mimic gastric acid secretion rate. The performance of the modified dissolution  apparatus was compared with USP dissolution. Apparatus 2 (paddle): the problem of adherence of the tablet to the shaft of the paddle was observed with the USP dissolution apparatus. The tablet did not stick to the agitating device in the proposed dissolution curves was observed between the USP method and the proposed method at 10% difference level (f2=57). The proposed test may show good in vitro-in vivo correlation since an attempt is made to mimic the in vivo conditions such as gastric volume, gastric emptying, and gastric acid secretion rate. Dissolution testes are performed using dissolutions apparatus, samples are withdrawn periodically from the dissolution medium with replacement and the analyzed for their drug content after an appropriate dilution

 

X-ray/ gamma scintigraphy:

X-ray/ gamma scintigraphy is a very popular evaluation parameter  for floating dosage form now a days. It helps to locate dosage from in 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 visualized by x-rays. similarly ,the inclusion of a γ-emitting radionuclide in a formulation allows indirect external observation using a γ-camera or scinti-scanner. In case of γ-scintigraphy, the γ-rays emitted by the radionuclide are focused on a camera, which helps to monitor  the location of the dosage form in the GI tract

 

Formulation   of   FDDS41: 

Polymers:

The  following   polymers  used  in  preparations  of  floating  drugs -  HPMC K4,  HPMC  K4  M, HPMC K15, calcium  alginate, eudragit s100,  eudragit RL, Mthocel  K4M,  polyethylene   oxide,  a  cyclodextrin , HPMC, CMC, polyethyleneglycol, polycarbonate, PVA, polycarbonate, sodium  alginate,  HPC-L,  CP 934P,   HPC,  Eudragit RS,  ethyl  cellulose,  poly   methyl   methacrylate , PVP, HPC-H,  HPC-M, polyox, acrylic  polymer E4M and carbopol.

 

 

 

Sustained release polymers:

These are the polymers which are used for sustained release action. E.g, HPMC, polycarbonate, polyethylene glycol, sodium alginate, carbopol, eudragit

 

Effervescent generating system:

Citric acid, tartaric acid, sodium bicarbonate,  citroglycine etc

 

Hydro colloids:

Suitable hydrocolloids are synthetics, anionic or non ionic like hydrocolloids are synthetics, cellulose derivatives. E.g. Accasia, pectin, agar, alginates, gelatin, casein, bentonite, veegum, HPC, HEC, and sodium CMC can be used. the hydrocolloids must hydrate in acidic fluid is having pH 1.2. Although the bulk  density of the formulation may initially be more than one, but when gastric fluid is enter in the system, it should be hydro-dynamically balanced to have a bulk density of less than one to assure buoyancy

 

Inert fatty materials:

Edible, pharmaceutical inert fatty material, having a specific gravity less than one can be added to formulation to decrease the hydrophilic property of formulation and hence increases the buoyancy. Eg. Purified grades of beeswax, fatty acids, long chain alcohols , glycerides and mineral oils can be used.

 

Release rate accelerates:

The release rate of the medicament from the formulation can be modified by including excipient like lactose and /or mannitol. These may be present from about 5-60% by weight

 

Release rate retardant:

Insoluble substance such as di-calcium phosphate , talc, magnesium state decreased the solubility and hence retard the release of medicaments

 

Buoyancy increasing agents:

Materials like  ethyl cellulose, which has bulk density less than one, can be used for enhancing the buoyancy of the formulation. It may be adapted up to 80% by weight

 

Low  density material:

Polypropylene foam powder

 

Miscellaneous:

Pharmaceutically acceptable adjuvant like preservatives, stabilizers, and  lubricants can  be incorporates  in the dosage forms as per the requirements . they do not adversely affect the hydrodynamic balance of systems.

 

 

 

 

Applications of FDDS 42, 43:

 

Sustained drug delivery:

Oral CR formulations are encountered with problems such as gastric residence time in the GIT. These problems can be overcome with the HBS systems which can remain in the stomach for long periods and have bulk density <1 as a result of which they can float on the gastric contents. These systems are relativity larger in size and passing from the pyloric opening is  prohibited.

 

Site-specific drug delivery:

These systems are particularly advantages for that are specifically absorbed from stomach or the proximal part of the small intestine , e.g, riboflavin and furosemide is primarily absorbed from the stomach followed by the duodenum. It has been reported that a monolithic floating dosage form with prolonged gastric residence time was developed and the bioavailability was increased. AUC obtained with the floating tablets was approximately 1.8 times those of conventional furosemide  tablets

 

Absorption or bioavailability enhancement:

Drugs that have poor bioavailability because of site-specific absorption from the upper part of the gastrointestinal tract are potential candidates to be formulated as floating drug delivery systems, thereby maximizing their absorption . A significant increase in the bio-availability of floating dosage forms (42.9%)could be achieved as compared with commercially available LZASIX tablets  (33.4%) and enteric-coated LASIX-long product (29.5%)

 

Reduced fluctuations of drug  concentration:

Continuous input of the drug following CR-GRDF administration produces blood drug contractions within a narrower range compared to the immediate dosage forms. Thus, fluctuations in the drug effects 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

 

CONCLUSION:

Drug absorption in the gastrointestinal tract is highly variable procedure and prolonging gastric retention of the dosage form extends the time for drug adsorption. FDDS promises to be a potential approach for gastric retention. Although there are number of difficulties to be worked out to achieve prolonged gastric retention, a large number of companies are focusing toward commercializing this technique.

 

 

 

 

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33.   Ashok Thulluru, S. Shakir Basha, C. Bhuvaneswara Rao, Ch. S. Phani Kumar, Nawaz Mahammed, K. Saravanakumar. Optimization of HPMC K100M and sodium alginate ratio in Metronidazole Floating Tablets for the Effective Eradication of Helicobacter pylori.  Asian Journal of Pharmacy and Technology. 2019; 9(3): 195-203.

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37.   Ashok Thulluru, M. Mohan Varma, C. M. Setty. Formulation and in vitro Evaluation of Tolperisone HCl Gastro retentive floating tablets. Journal of pharmacy and chemistry. 2016; 10(2): 31-38.

38.   Raju DB, Sreenivas R and Varma MM. Formulation and evaluation of floating drug delivery system of Metformin Hydrochloride. J Chem Pharm Res. 2010; 2(2): 274-78.

39.   Ashok Thulluru, M. Mohan Varma, C. M. Setty, A. Anusha, P. Chamundeeswari, Sk. Sanufar. Formulation, in vitro and in vivo Evaluation of Pioglitazone Hydrochloride - Effervescent Gastro Retentive Floating Hydrophilic Matrix Tablets. International Journal of Pharm Tech Research. 2016; 9(7): 388-98.

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41.   Ashok Thulluru, Janga Mary Sushma. Optimization of HPMC K100M and HPMC K4M Ratio in Extending the Release of Valacyclovir HCl from its Gastro Retentive Floating Tablet. Inventi Rapid: Novel Excipients. 2016 (1): 1-8, 2015.

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Received on 13.12.2019            Modified on 16.01.2020

Accepted on 05.02.2020      ©Asian Pharma Press All Right Reserved

Asian J. Pharm. Res. 2020; 10(1): 39-47.

DOI: 10.5958/2231-5691.2020.00009.X