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Chanda R et al /Int.J. PharmTech Res.

2010,2(1) 49

International Journal of PharmTech Research


CODEN (USA): IJPRIF ISSN: 0974-4304
Vol.2, No.1, pp 49-59, Jan-Mar 2010

FLOATING DRUG DELIVERY:


A POTENTIAL ALTERNATIVE TO CONVENTIONAL
THERAPY

Chanda R*1, Roy A2, Bahadur S2, Saha S2, Das S3, Choudhury A3
1
Bengal School of Technology, Sugandha, Delhi Road, Hooghly-712102, (W.B), India
2
Columbia Institute of Pharmacy, Tekari, Near Vidhan Sabha, Raipur 493111, (C.G), India
3
GRY Institute of Pharmacy, Vidya Vihar, Borawan, Khargone 451228 (M.P), India
*E. mail: ranabirchanda@yahoo.com

ABSTRACT: Conventional dosage forms not only produce rapid and relatively high peak blood levels resulting in
adverse effects but also should be administered rapidly. To overcome these drawbacks many rate-controlled oral drug
delivery systems have been developed. These new dosage forms can overcome physiological adversities, such as short
gastric residence times (GRT) and unpredictable gastric emptying times (GET). Several approaches are currently utilized
in the prolongation of the GRT, including floating drug delivery systems (FDDS), providing opportunity for both local
and systemic drug action. This paper aims to review the development in the floating drug delivery systems to provide
basic principles to the young scientists and scholars, which will be useful to circumvent the difficulties associated with
formulation design.
KEYWORDS: floating drug, buoyancy mechanism, pharmacokinetic advantages.
intervals, but also increase patient compliance beyond
INTRODUCTION the level of existing controlled release dosage forms.
Oral delivery of drugs is by far the most preferable This application is especially effective in delivery of
route of drug delivery due to the ease of sparingly soluble and insoluble drugs. It is known that,
administration, patient compliance and flexibility in as the solubility of a drug decreases, the time available
formulation, etc. From immediate release to site- for drug dissolution becomes less adequate and thus
specific delivery, oral dosage forms have really the transit time becomes a significant factor affecting
progressed. However, it is a well-accepted fact that it drug absorption. To address this, oral administration of
is difficult to predict the real in-vivo time of release sparingly soluble drugs is carried out frequently, often
with solid, oral controlled-release dosage forms. Thus, several times per day.2
drug absorption in the gastrointestinal (GI) tract may Gastric retention will provide advantages such as the
be very short and highly variable in certain delivery of drugs with narrow absorption windows in
circumstances. It is evident from the recent scientific the small intestinal region. Also, longer residence time
and patent literature that an increased interest in novel in the stomach could be advantageous for local action
dosage forms that are retained in the stomach for a in the upper part of the small intestine, for example
prolonged and predictable period of time exists today treatment of peptic ulcer disease. Furthermore,
in academic and industrial research groups. One of the improved bioavailability is expected for drugs that are
most feasible approaches for achieving a prolonged absorbed readily upon release in the GI tract. These
and predictable drug delivery profile in the GI tract is drugs can be delivered ideally by slow release from the
to control the gastric residence time (GRT). Dosage stomach. Many drugs categorized as once-a-day
forms with a prolonged GRT, i.e.gastroretentive delivery have been demonstrated to have suboptimal
dosage forms (GRDFs), will provide us with new and absorption due to dependence on the transit time of the
important therapeutic options.1 GRDFs extend dosage form, making traditional extended release
significantly the period of time over which the drugs development challenging. Therefore, a system
may be released. Thus, they not only prolong dosing designed for longer gastric retention will extend the
Chanda R et al /Int.J. PharmTech Res.2010,2(1) 50

time within which drug absorption can occur in the iii. drugs that are poorly soluble at an
small intestine. Certain types of drugs can benefit from alkaline pH;
using gastric retentive devices. These include: iv. drugs with a narrow window of
i. drugs acting locally in the stomach; absorption;
ii. drugs that are primarily absorbed in v. drugs absorbed rapidly from the GI
the stomach; tract; and
vi. drugs that degrade in the colon.3

BIOLOGICAL ASPECTS OF GRDFS


Physiology of Stomach

Figure 1: Diagram of human stomach

The GI tract is essentially a tube about nine metres stomach as well as the rest of the GI tract. The GI tract
long that runs through the middle of the body from the is in a state of continuous motility consisting of two
mouth to the anus and includes the throat (pharynx), modes: interdigestive motility pattern and digestive
oesophagus, stomach, small intestine (consisting of the motility pattern. The former is dominant in the fasted
duodenum, jejunum and ileum) and large intestine state with a primary function of cleaning up the
(consisting of the cecum, appendix, colon and rectum). residual content of the upper GI tract. The
The wall of the GI tract has the same general structure interdigestive motility pattern is commonly called the
throughout most of its length from the oesophagus to ‘migrating motor complex’ (‘MMC’) and is organized
the anus, with some local variations for each region. in cycles of activity and quiescence. Each cycle lasts
The stomach is an organ with a capacity for storage 90–120 minutes and consists of four phases. The
and mixing. The antrum region is responsible for the concentration of the hormone motilin in the blood
mixing and grinding of gastric contents. Under fasting controls the duration of the phases.4
conditions, the stomach is a collapsed bag with a In the interdigestive or fasted state, an MMC wave
residual volume of approximately 50ml and contains a migrates from the stomach down the GI tract every
small amount of gastric fluid (pH1–3) and air. The 90–120 minutes. A full cycle consists of four phases,
mucus spreads and covers the mucosal surface of the beginning in the lower esophageal sphincter/gastric
Chanda R et al /Int.J. PharmTech Res.2010,2(1) 51

pacemaker, propagating over the whole stomach, the emptying and that the floating units remained buoyant
duodenum and jejunum, and finishing at the ileum. on gastric fluids. These are less likely to be expelled
Phase III is termed the ‘housekeeper wave’ as the from the stomach compared with the nonfloating units,
powerful contractions in this phase tend to empty the which lie in the antrum region and are propelled by the
stomach of its fasting contents and indigestible debris. peristaltic waves. Several formulation parameters can
The administration and subsequent ingestion of food affect the gastric residence time. More reliable gastric
rapidly interrupts the MMC cycle, and the digestive emptying patterns are observed for multiparticulate
phase is allowed to take place. The upper part of the formulations as compared with single unit
stomach stores the ingested food initially, where it is formulations, which suffer from “all or none concept”.
compressed gradually by the phasic contractions. The The units of multiparticulate systems are distributed
digestive or fed state is observed in response to meal freely throughout the gastrointestinal tract.
ingestion. It resembles the fasting Phase II and is not The most important parameters affecting gastric
cyclical, but continuous, provided that the food emptying and, hence, the gastric retention time of oral
remains in the stomach. Large objects are retained by dosage forms include:
the stomach during the fed pattern but are allowed to i. Density – GRT is a function of dosage form
pass during Phase III of the interdigestive MMC. It is buoyancy that is dependent on the density;
thought that the sieving efficiency (i.e. the ability of ii. Size – dosage form units with a diameter of
the stomach to grind the food into smaller size) of the more than 7.5mm are reported to have an
stomach is enhanced by the fed pattern and/or by the increased GRT compared with those with a
presence of food. The fasted-state emptying pattern is diameter of 9.9mm;
independent of the presence of any indigestible solids iii. Shape of dosage form – tetrahedron and ring
in the stomach. Patterns of contractions in the stomach shaped devices with a flexural modulus of 48
occur such that solid food is reduced to particles of and 22.5 kilo pounds per square inch (KSI) are
less than 1mm diameter that are emptied through the reported to have better GRT ≈ 90% to 100%
pylorus as a suspension. The duration of the retention at 24 hours compared with other
contractions is dependent on the physiochemical shapes;
characteristics of the ingested meal. Generally, a meal iv. Single or Multiple unit formulation –
of ~450kcal will interrupt the fasted state motility for multiple unit formulations show a more
about three to four hours. It is reported that the antral predictable release profile and insignificant
contractions reduce the size of food particles to ≤1mm impairing of performance due to failure of
and propel the food through the pylorus. However, it units, allow co-administration of units with
has been shown that ingestible solids ≤7mm can empty different release profiles or containing
from the fed stomach in humans.5 incompatible substances and permit a larger
margin of safety against dosage form failure
Gastric residence time (GRT) and its effect compared with single unit dosage forms;
Gastric residence time of an oral dosage form is v. Fed or Unfed state – under fasting conditions,
affected by several factors. To pass through the pyloric the GI motility is characterized by periods of
valve into the small intestine the particle size should be strong motor activity or the migrating
in the range of 1 to 2 mm. The pH of the stomach in myoelectric complex (MMC) that occurs every
fasting state is ~1.5 to 2.0 and in fed state is 2.0 to 6.0. 1.5 to 2 hours. The MMC sweeps undigested
A large volume of water administered with an oral material from the stomach and, if the timing of
dosage form raises the pH of stomach contents to 6.0 administration of the formulation coincides
to 9.0. Stomach doesn’t get time to produce sufficient with that of the MMC, the GRT of the unit can
acid when the liquid empties the stomach; hence be expected to be very short. However, in the
generally basic drugs have a better chance of fed state, MMC is delayed and GRT is
dissolving in fed state than in a fasting state. The considerably longer;
resting volume of the stomach is 25 to 50 ml. Volume vi. Nature of meal – feeding of indigestible
of liquids administered affects the gastric emptying polymers or fatty acid salts can change the
time. When volume is large, the emptying is Faster. 6 motility pattern of the stomach to a fed state,
Fluids taken at body temperature leave the stomach thus decreasing the gastric emptying rate and
faster than colder or warmer fluids. Studies have prolonging drug release;
revealed that gastric emptying of a dosage form in the vii. Caloric content – GRT can be increased by
fed state can also be influenced by its size. Small-size four to 10 hours with a meal that is high in
tablets leave the stomach during the digestive phase proteins and fats;
while the large-size tablets are emptied during the viii. Frequency of feed – the GRT can increase by
housekeeping waves. over 400 minutes when successive meals are
According to the current research the effect of size of given compared with a single meal due to the
floating and nonfloating dosage forms on gastric low frequency of MMC;
Chanda R et al /Int.J. PharmTech Res.2010,2(1) 52

ix. Gender – mean ambulatory GRT in males content needed to allow the proper achievement of the
(3.4±0.6hours) is less compared with their age buoyancy retention principle, a minimal level of
and race matched female counterparts (4.6±1.2 floating force (F) is also required to keep the dosage
hours), regardless of the weight, height and form reliably buoyant on the surface of the meal. To
body surface); measure the floating force kinetics, a novel apparatus
x. Age – elderly people, especially those over 70, for determination of resultant weight (RW) has been
have a significantly longer GRT; reported in the literature. The RW apparatus operates
xi. Posture – GRT can vary between supine and by measuring continuously the force equivalent to F
upright ambulatory states of the patient; (as a function of time) that is required to maintain the
xii. Concomitant drug administration – submerged object. The object floats better if RW is on
anticholinergics like atropine and the higher positive side (Fig. 2b). This apparatus helps
propantheline, in optimising FDDS with respect to stability and
Opiates like codeine and prokinetic agents like durability of floating forces produced in order to
metoclopramide Nand cisapride; and prevent the drawbacks of unforeseeable intragastric
xiii. Biological factors – diabetes and Crohn’s buoyancy capability variations.
disease, etc.7
RW or F = F buoyancy - F gravity = (Df - Ds) gV,
Where RW = total vertical force, Df = fluid density,
FLOATING DRUG DELIVERY SYSTEMS Ds = object density, V = volume and g = acceleration
(FDDS) due to gravity.8

Floating drug delivery systems (FDDS) have a bulk Several approaches are currently used to prolong the
density less than gastric fluids and so remain buoyant gastric retention time. These include floating drug
in the stomach without affecting the gastric emptying delivery systems also known as hydro dynamically
rate for a prolonged period of time. While the system balanced systems, swelling and expanding systems,
is floating on the gastric contents (Fig. 2a), the drug is polymeric bio-adhesive systems, modified shape
released slowly at the desired rate from the system. systems, high density systems and other delayed
After release of drug, the residual system is emptied gastric emptying devices. The principle of buoyant
from the stomach. This results in an increased GRT preparation offers a simple and practical approach to
and a better control of the fluctuations in plasma drug achieve increased gastric residence time for the dosage
concentration. However, besides a minimal gastric form and sustained drug release. 9

Figure 2: The Mechanism of Floating Systems

Background for development of FDDS Many therapeutic agents ate metabolized in the upper
GI tract into an active form. This active form is then
Chanda R et al /Int.J. PharmTech Res.2010,2(1) 53

through the wall intestine. The therapeutic agents ate Technologies based on buoyancy mechanism for
metabolized by enzymes in the upper GI tract. If the FDDS:
therapeutic agent is present in large quantities, i. Effervescent Floating Drug Delivery System
saturation of these enzymes can occur with the result ii. Non- Effervescent Floating Drug Delivery
that most of the therapeutic agent passes through the System
GI tract therefore limits the potency of the therapeutic
agent. Effervescent Floating Drug Delivery System
Conventional controlled release dosage forms have a These Buoyant Delivery System are Prepared with
density greater than that of gastric contents, thus these swellable polymers such as methocel or
dosage forms sink to the bottom of the stomach once polysaccharides e.g. chitiosan and effervescent
ingested. The de novo design of oral controlled drug component e.g. sodium bicarbonate citric or tartaric
systems (DDS) is known in the art to achieve more acid or matrices containing chambers of liquid that
predictable bioavailability of drugs. However, it is gasify at body temperature.
well known that conventional release DDS do not The matrices are fabricated so that upon contact with
Overcome adversities such as gastric residence time gastric fluid, carbon dioxide is liberated by the acidity
(GST) and gastric empty time (GET). Gastric of gastric contents and is entrapped in the gellified
emptying is the process by the fasted stomach exhibits hydrocolloid. This produces an upward motion of the
a cyclic activity called the inter-digestive migrating dosage form and maintains its buoyancy. The carbon
motor complex (IMMC). The purpose of this cycle is dioxide generating components may be intimately
to migrate the contents of the stomach through the mixed within the tablet matrix to produce a single-
pyloric sphincter although ingestion of food interrupts layered tablet or a bi-layered tablet may be compressed
the cycle. which contains the gas generating mechanism in one
One approach to overcome the adversities of GRT and hydrocolloid containing layer and the drug in the other
GET is the floating system also known as layer formulated for the SR effect.
hydrodynamically balanced systems. These systems The floating dosage forms are kept in the stomach for
are expected to remain lastingly buoyant on the gastric extended periods of time the therapeutic agents are not
contents without affecting the intrinsic rate of immediately released after ingestion. Controlled
emptying because their bulk density is lower than that release of such therapeutic agents from the dosage
of the gastric fluids. The floating forms maintain their forms prevents enzyme saturation thereby improving
low density value while the polymer hydrates and the bioavailability of such therapeutic agents. So,
forms a gel. The drug is progressively release from the it improves the bioavailability of by administering
swollen matrix in the case of conventional hydrophilic such therapeutic agent in a floating dosage from.
matrices. 10

Figure 3: Working principle of effervescent floating drug delivery system .

Non- Effervescent Floating Drug Delivery System polystyrene. One of the approaches to the formulation
Commonly used excipients, here are gel-forming or of such floating dosage forms involves intimate mixing
highly swellable cellulose type hydrocolloids, of drug with a gel forming hydrocolloid which swells
polysaccharides and matrix forming polymers such as in contact with gastric fluid after oral administration
polycarbonate, polyacrylate, polymethacrylate and and maintains a relative integrity of shape and a bulk
Chanda R et al /Int.J. PharmTech Res.2010,2(1) 54

density of less than unity within the outer gelatinous matter of seconds) when immersed in water. Oral drug
barrier. delivery formulations made from the gels would swell
The air entrapped by the swollen polymer confers rapidly in the stomach, causing medications to move
buoyancy to these dosage forms. The gel structure acts more slowly from the stomach to the intestines and be
as a reservoir for sustained drug release since the drug absorbed more efficiently by the body. Drugs reported
is slowly released for sustained drug release since the to be used in the formulation of floating dosage forms
drug is slowly released by a controlled diffusion are floating microspheres (aspirin, griseofulvin, p-
through the gelatinous barrier. Other approaches nitroaniline, ibuprofen, terfinadine and tranilast),
reported in the literature are hydrodynamically floating granules (diclofenac sodium, indomethacin
balanced systems(HBS) developed by Sheth and and prednisolone), films (cinnarizine), floating
Tossounian, which contain a mixture of drug and capsules (chlordiazepoxide hydrogen chloride,
hydrocolloids, sustained release capsules containing diazepam, furosemide, misoprostol, L-Dopa,
cellulose derivatives like starch and a higher fatty benserazide, ursodeoxycholic acid and pepstatin) and
alcohol or fatty acid glyceride, bilayer compressed floating tablets and pills (acetaminophen,
capsules, multilayered flexible sheet-like medicament acetylsalicylic acid, ampicillin, amoxycillin trihydrate,
devices, hollow microspheres of acrylic resins, atenolol, diltiazem, fluorouracil, isosorbide
polystyrene floatable shells, single and multiple unit mononitrate, para- aminobenzoic acid, piretamide,
devices with floatation chambers and microporous theophylline and Verapamil hydrochloride, etc.).
compartments and buoyant controlled release powder Excipients used most commonly in these systems
formulations, etc. Recent developments include use of include HPMC, polyacrylate polymers, polyvinyl
superporous hydrogels that expand dramatically acetate, Carbopol, agar, sodium alginate, calcium
(hundreds of times their dehydrated form within a chloride, polyethylene oxide and polycarbonates. 9, 11-14

Figure 4: Mechanism of hydrodynamically balanced system

Advantages of floating drug delivery system gastro retentive product or a product which has
i. This type of drug delivery systems is an enhanced retention time in the stomach.
especially very useful in the treatment of the ii. All those molecules with considerably short
disorders related to the stomach. As the prime half life can be administered in this manner to
objective of such systems is to produce a get an appreciable therapeutic activity.
Chanda R et al /Int.J. PharmTech Res.2010,2(1) 55

iii. This is a primary manner in which the


bioavailability of a therapeutic agent can be Idiosyncratic factors
enhanced especially all those drugs which get The concomitant intake of food and drugs such as
metabolized in the upper GIT. anticholinergics (e.g., atropine or propantheline),
iv. They also have an advantage over the opiates (e.g., codeine) and prokinetic agents (e.g.,
conventional system as it can be used to metoclopramide and cisapride), may affect the
overcome the adversities of gastric retention performance of GRDDS. The co administration of GI
time as well as the gastric emptying time, as motility–decreasing drugs can increase gastric
these systems are expected to remain buoyant emptying time. On the contrary, these drugs should be
on the gastric fluid without affecting the contraindicated with mucoadhesive systems because
intrinsic rate of emptying because their bulk they reduce gastric secretion and induce the drying of
density is lower than that of the gastric fluids. mucus membranes.21
v. The duration of treatment through a single Biological factors such as gender, age, posture, body
dose, that releases the active ingredient over mass index, and disease state (e.g., diabetes or Crohn’s
an extended period of time. disease) also may affect gastro retention. For example,
vi. The active entity is delivered to the site of women and the elderly show slower gastric emptying
action, thus minimizing or eliminating the side than do men and younger subjects. Intrasubject and
effects.15 intersubject variations also are observed in gastric and
intestinal transit times.
FACTORS AFFECTING FDDS PERFORMANCE GRT increases in the presence of food, leading to
Formulation factors increased drug dissolution and longer residence of the
The shape of the dosage form is one of the factors that dosage form at the most favorable site of absorption.
affect its GRT16. Six shapes (ring, tetrahedron, Furthermore, the nature, caloric content, and the
cloverleaf, string, pellet, and disk) were screened in frequency of food intake affect the GRT of the dosage
vivo for their gastric retention potential. The form (18, 23). A GRT of 4–10 h has been reported after
tetrahedrons (each leg 2 cm long) and rings (3.6 cm in a meal of fats and proteins. 22 The presence of food in
diameter) exhibited nearly 100% retention at 24 h. On the stomach affects a floating system’s ability to
the other hand, cloverleaves (2.2–3.2 cm in diameter) maintain an intragastric position distant from the
exhibited 40–67% retention; discs (2.5 cm diameter), gastroduodenal junction, which appears to prevent
67%; string (12 cm x 2 mm x 2 mm/24 cm x 2 mm x 2 early and erratic emptying during the digestive phases.
mm), 0%; and pellets (4 mm), 0% retention at 24 h. The buoyancy of floating dosage forms enables their
Size also can determine how long a dosage form is retention for more than 6 h in the fed state.23
retained in the stomach. Small tablets are emptied from Subject posture (e.g., standing or supine) also leads to
the stomach during the digestive phase, but large ones variable intragastric behaviors. An upright position
are expelled during the housekeeping waves. 17 Various protects floating forms against postprandial emptying
gastric emptying times were observed for because the floating form remains above the gastric
nondisintegrating tablets of different sizes. 18 The contents irrespective of its size. 24 In subjects positioned
longest gastric emptying time was observed for 13-mm upright, floating dosage forms show prolonged and
tablets (171 ± 13 min), followed by 11-mm (128 ± 17 more reproducible GRTs than conventional dosage
min) and 7-mm (116 ± 19 min) tablets. These results forms.25 The conventional dosage forms sink to the
are in accordance with the aperture of the resting lower part of the distal stomach where they are
pylorus, 12.8 ± 7 mm,19 which can be taken as the expulsed through the pylorus by antral peristaltic
critical value for GI transit of dosage forms of different waves.
sizes. In the case of floating systems, however, no In supine subjects, large dosage forms (both
statistically significant difference exists in the extent of conventional and floating) experience prolonged
gastric retention among dosage forms of different retention. After the ingestion of meals, conventional
sizes, which confirms that intragastric buoyancy is the dosage forms sink and are deposited toward the
main determinant of prolonged residence in the posterior gastric wall. This position offers no reliable
stomach. protection against early and erratic emptying. The
In the case of floating systems, formulation variables gastric retention of these dosage forms is therefore
such as the viscosity grade of the polymers and their directly related to their size. On the other hand,
interactions significantly affect floating properties of floating forms appear to be equally likely to remain
the delivery system and drug release. Low-viscosity buoyant anywhere between the lesser and greater
polymers (e.g., HPMC K100 LV) were found to be curvatures of the stomach. On moving distally, these
more beneficial than high-viscosity polymers (e.g., units may be swept away by the contractile waves that
HPMC K4M) in improving floating properties. In propel the gastric contents towards the pylorus, leading
addition, a decrease in the release rate was observed to significant reduction in GRT compared with upright
with an increase in polymer Viscosity.20 subjects. Therefore, patients preferably should not be
Chanda R et al /Int.J. PharmTech Res.2010,2(1) 56

dosed with a floating drug delivery system just before will float, the density value does not reflect the
going to bed. magnitude of floating forces produced by the object. 32
Moreover, a single density determination made before
EVALUATION OF FDDS immersion does not predict the floating force evolution
Any drug product must be evaluated to ensure its of the dosage form because the dry material of which it
performance characteristics and to control batch-to- is made progressively reacts or interacts within the
batch quality. In addition to routine tests for general gastric fluid to release its drug contents. Therefore, an
appearance, hardness, friability, drug content, weight in vitro measuring apparatus has been conceived to
variation, uniformity of content, disintegration time, determine the real floating capabilities of buoyant
and drug release, the gastroretentive performance of dosage forms as a function of time. It operates by
FDDS must be evaluated. 26 measuring the force equivalent to the force F required
to keep the object totally submerged in the fluid. This
Floating/buoyancy time force determines the resultant weight of the object
The test for buoyancy is usually determined in 900 mL when immersed and may be used to quantify its
of simulated gastric (HCl/NaCl with 0.02% Tween 80, floating or nonfloating capabilities. The magnitude and
pH 1.2) or intestinal fluids (KH 2PO4/NaOH buffer with direction of the force and the resultant weight
0.02% Tween 80, pH 7.4) maintained at 37 ᵒC using corresponds to the vectorial sum of buoyancy (F buoy)
the USP dissolution apparatus. These fluids simulate and gravity (Fgrav) forces acting on the object as shown
the surface tension of human gastric juice (35–50 in the equation,
mN/m2). 27 The amount of time the dosage form floats
is termed the floating time.11 In the case of floating F = F buoy - F
microparticles, the number of floating particles and the F = df gV - ds gV = (df - ds) gV
time during which they remain buoyant on the test
solution can be determined.28,29 The floating process F - (df - M/V) gV
depends on the balance between the weight and
volume of the dosage form. An increase in the where F is the total vertical force (resultant weight of
buoyancy force caused by the increased volume causes the object), g is the acceleration due to gravity, df is the
a resultant weight increase and leads to dosage-form fluid density, ds is the object density, M is the object
flotation.30 mass, and V is the volume of the object.8 By
convention, a positive resultant weight signifies that
Specific gravity the force F is exerted upward and that the object is able
The specific gravity of floating systems can be to float, whereas a negative resultant weight means
determined by the displacement method, using that F acts downward and that the object sinks (Fig.5).
benzene as a displacing medium. 31 The crossing of the zero base line by the resultant
Resultant weight weight curve from positive toward negative values
Until now, bulk density and floating duration have indicates a transition of the dosage form from floating
been the main parameters to describe the adequacy of a to nonfloating conditions. The intersection of lines on
dosage form’s buoyancy. However, although the a time axis corresponds to the floating time of the
density value may indicate whether or not an object dosage form.

Figure 5: Effect of resultant weight during buoyancy on the floating tendency of FDDS
Chanda R et al /Int.J. PharmTech Res.2010,2(1) 57

PHARMACOKINETIC ADVANTAGES AND drug level being reached in this area, and might lead to
FUTURE POTENTIAL better treatment of peptic ulcer disease.
As sustained release systems, floating dosage forms
offer various potential advantages from several recent LIMITATION
publications. Drugs that have poor bioavailability One of the disadvantages of floating systems is that
because their absorption is restricted to the upper GI they require a sufficiently high level of fluids in the
tract can be delivered efficiently thereby maximizing stomach for the drug delivery buoy to float therein and
their absorption and improving their absolute to work efficiently. However, this limitation can be
bioavailabilities. For instance, a significant increase in overcome by coating the dosage form with bioadhesive
the absolute bioavailability of the floating dosage form polymers, thereby enabling them to adhere to the
of furosemide has been obtained (42.9%), compared to mucous lining of the stomach wall alternatively, the
the commercial available tablet (Lasix; 33.4%) and dosage form may be administered with a glass full of
enteric product (Lasix long; 29.5%).33 Furthermore, water (200–250 ml). Floating systems are not feasible
among these three dosage forms, only the floating for those drugs that have solubility or stability
dosage form yielded satisfactory in vitro results that problems in gastric fluids. Drugs such as nifedipine,
were significantly correlated (P<0.05) within vivo which is well absorbed along the entire GI tract and
absorption kinetics. The findings of this study were which undergoes significant first-pass metabolism,
based on a previous postulation that site-specific may not be desirable candidates for FDDS since the
absorption and longer GRT could possibly increase the slow gastric emptying may lead to reduced systemic
bioavailability of furosemide.34 bioavailablity. Also there are limitations to the
Similar observations were made by Ichikawa et al.35 applicability of FDDS for drugs that are irritants to
who found that floating pills containing p- gastric mucosa.40
aminobenzoic acid, a drug with a limited absorption
site in the GI tract, had 1.61 times greater AUC than CONCLUSION
the control pills(32.29±66.06 vs.20.10±65.8 mg.h/ml). The currently available polymer-mediated non-
These authors, however, did not find any significant effervescent and effervescent FDDS, designed on the
difference in bioavailabilty of isosorbide-5-nitrate basis of delayed gastric emptying and buoyancy,
when floating and control pills were compared. This appear to be an effective and rational approach to the
difference in results could be explained by the fact that modulation of controlled oral drug .This is evident
isosorbide-5-nitrate is well absorbed from both the from the number of commercial products and a myriad
stomach and small intestine. Thus prolonging the GRT of patents issued in this field. The FDDS become an
of a dosage form offer no advantage (in terms of additional advantage for drugs that are absorbed
bioavailability) for drugs with multiple absorption sites primarily in the upper segments of GI tract, i.e., the
in the GI tract. Developing controlled release systems stomach, gastric duodenum, and jejunum. Some of the
for such drugs as bromocriptine might lead to unresolved critical issues related to the rational
treatment of Parkinson’s disease. After oral development of FDDS include,
administration, approximately 30% of the dose is
absorbed from the GI tract. 36 However, its low i. The quantitative efficiency of floating
absorption potential, which often results from low dose delivery systems in the fasted and fed
usage, be improved by a HBS dosage form, which states;
could significantly enhance its therapeutic efficacy. 37 ii. The role of buoyancy in enhancing
Another therapeutic area in which FDDS can be GRT of FDDS; and
explored is the eradication of Helicobacter pylori, iii. The correlation between prolonged
which is now believed to be the causative bacterium GRT and SR/PK characteristics.
for chronic gastritis and peptic ulcers. Although the Finally, with an increasing
bacterium is highly sensitive to most antibiotics, its understanding of polymer behavior
eradication from patients requires high concentrations and the role of the biological factors, it
of drug be maintained within the gastric mucosa for a is suggested that future research work
long duration.38 Recently Katayama et al.39 developed in the floating drug delivery systems
a SR liquid preparation of ampicillin using sodium should be aimed at discovering means
alginate that spreads out and adheres to the gastric to accurately control the drug input
mucosal surface whereby the drug is continuously rate into the GI tract for the
released. Thus it can be expected that topical delivery optimization of the pharmacokinetic
of a narrow spectrum antibiotic through a FDDS may and toxicological profiles of medicinal
result incomplete removal of the organisms in the agents.
fundal area of the gastric mucosa due to bactericidal
Chanda R et al /Int.J. PharmTech Res.2010,2(1) 58

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