Академический Документы
Профессиональный Документы
Культура Документы
Review Article
Floating Drug Delivery Systems: A critical analysis
Author: Sudhir Pandya
NuLife Pharmaceuticals, Pimpri, Pune, MS, India. Pin- 411018
Email: pandyasudhir@hotmail.com
ABSTRACT
Oral controlled drug delivery systems should be designed in order to achieve more predictable
and increased bioavailability of drugs. Sophisticated oral dosage forms such as controlled drug
delivery systems are playing major role. Such systems release drug at predetermined rate, as
determined by drug pharmacokinetics and desired therapeutic concentration. While optimizing
the delivery systems physiological challenges, such as short gastric residency, varying gastric
emptying and other factors are always the point of focus. Approaches that are currently utilized
in the prolongation of the gastro residency include floating drug delivery systems (FDDS),
swelling and expanding systems, polymeric bioadhesive systems, high-density systems,
modified-shape systems and other delayed gastric emptying devices. It is evident from the recent
scientific and patent literature that an increased interest in novel dosage forms that are retained in
the stomach for a prolonged and predictable period of time exists today in academic and
industrial research groups. One of the most feasible approaches for achieving a prolonged and
predictable drug delivery profile in the GI tract is to control the gastric residence time (GRT).
Dosage forms with a prolonged GRT, i.e. gastro-retentive dosage forms (GRDFs), provide new
and important therapeutic options.
Keywords: floating drug delivery, oral drug delivery, and gastric emptying time, drug retention
http://www.pharmautility.com
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
INTRODUCTION
The design of an oral controlled drug delivery system should be primarily aimed at achieving
more predictable and increased bioavailability of drugs. Over the years, oral dosage forms have
become increasingly sophisticated with major role being played by controlled release drug
delivery systems. Such systems release drug at predetermined rate, as determined by drug
pharmacokinetics and desired therapeutic concentration.
The development of such systems is precluded by several physiological difficulties such as:
a. Inability to restrain and localise the drug delivery system within the desired range of
gastrointestinal tract and
b. Highly variable nature of gastric emptying process.
This variability may lead to unpredictable bioavailability and times to achieve peak plasma
levels, since the majority of drugs are preferentially absorbed in upper part of small intestine [1].
Gastric emptying time in humans is normally 2-3 hours through the major absorption zone
(stomach or upper part of the intestine), which may lead to incomplete drug release from the
dosage form resulting in diminished efficacy of administered dose. The intimate contact of the
drug delivery system (DDS) with the absorbing membrane has the potential to maximize drug
absorption and may also influence the rate of drug absorption [2, 3].
It is evident from the recent scientific and patent literature that an increased interest in novel
dosage forms that are retained in the stomach for a prolonged and predictable period of time
exists today in academic and industrial research groups. One of the most feasible approaches for
achieving a prolonged and predictable drug delivery profile in the GI tract is to control the
gastric residence time (GRT). Dosage forms with a prolonged GRT, i.e. gastro-retentive dosage
forms (GRDFs), provide new and important therapeutic options.
http://www.pharmautility.com
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
ADVANTAGES OF GRDFS
1. Sustained drug delivery:
Drug absorption from oral controlled release dosage forms is often limited by the short GRT
available for absorption. However, hydrodynamically balanced system (HBS) type forms
can remain in the stomach for several hours and, therefore, significantly prolong the GRT of
numerous drugs.
These special dosage forms are light, relatively large in size and do not easily pass through
the pylorus, which has an opening of approximately 0.9 1.9 cm [4]. It is worth noting here
that a prolonged GRT is not responsible for the slow absorption of a lipophilic drug such as
Isradipine that has been achieved with a floating modified-release capsule [5]. This is
because the major portion of drug release from modified-release capsule took place in the
colon, rather than in the stomach. However, the assumed prolongation in the GRT is
postulated to cause the sustained drug-release behaviour [6].
2. Site-specific drug delivery:
For drugs such as Furosemide and Riboflavin, which have limited absorption sites in the
small intestine rather than in the stomach, floating dosage form is a feasible approach. In
fact, the absorption of Furosemide has been found to be site-specific, the stomach being the
major site of absorption, followed by the duodenum [7].
This property prompted the development of a monolithic floating dosage form for
Furosemide, which could prolong the GRT, and thus its bioavailability was increased [8].
Recently, a bilayer floating capsule has been used to achieve local delivery of Misoprostol, a
synthetic prostaglandin E analog which is approved and marketed in the United States (as
http://www.pharmautility.com
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
Cytotec by Pharmacia United States of America) for prevention of gastric ulcers caused by
non-steroidal anti-inflammatory drugs [9].
Floating tablets containing 2050 mg of 5-fluorouracil have been successfully evaluated in
four patients with stomach neoplasms in which tablets floated in the stomach for period of 2
hours after administration [10].
3. Pharmacokinetic advantages:
Drugs that have poor bioavailability owing to their absorption from the upper Gastro
Intestinal (GI) tract can be delivered efficiently, thereby maximizing their absorption and
improving their absolute bioavailability. For instance, a significant increase in the absolute
bioavailability of the floating dosage form of Furosemide has been obtained (42.9%),
compared to the commercial available tablet (Lasix; 33.4% Aventis Pharmaceuticals Inc.)
and enteric product (Lasix long; 29.5% Aventis Pharmaceuticals Inc). [11]
The reduced fluctuations in the plasma levels of drugs result from delayed gastric emptying.
After oral dosing the bioavailability of standard Madopar (Levodopa and Benserazide,
Roche USA) was found to be 6070%; the difference in bioavailability of standard and HBS
formulations seems to be due to incomplete absorption rather than an altered disposition of
the drug [12].
Cook et al. demonstrated that a HBS capsule containing iron salts has an increased efficacy
and reduced side effects. Floating dosage forms with sustained release characteristic can also
be expected to reduce the variability in transit performance [13] and various
pharmacokinetic parameters [14]. It might be expected that developing HBS dosage form for
Tacrine might provide a better delivery system and reduce its GI side effects in Alzheimers
http://www.pharmautility.com
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
patients. In addition, buoyant delivery systems might provide a beneficial strategy for the
treatment of gastric and duodenal cancers [1]. The concept of Floating Drug Delivery
System (FDDS) has also been utilized in the development of various anti-reflux
formulations. (Figure 1)
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
removal of the organisms in the fundal area of the gastric mucosa due to bactericidal drug levels
being reached in this area, and might lead to better treatment of peptic ulcer disease.
LIMITATIONS
One of the disadvantages of floating systems is that they require sufficiently high level of fluids
in the stomach for the drug delivery to float therein and to work efficiently. However, this
limitation can be overcome by coating the dosage form with bio adhesive polymers, thereby
enabling them to adhere to the mucous lining of the stomach wall. Alternatively, the dosage form
may be administered with a glass full of water (200250 ml). Floating systems are not feasible
for those drugs that have solubility or stability problems in gastric fluids. Drugs such as
Nifedipine, which is well absorbed along the entire GI tract and which undergoes significant
first-pass metabolism, may not be a desirable candidate for FDDS, since the slow gastric
emptying may lead to reduced systemic bioavailability [1]. Also there are limitations to the
applicability of FDDS for drugs that irritate gastric mucosa.
MECHANISTIC APPROACHES OF FDDS
Various attempts have been made to retain the dosage form in the stomach as a way of
increasing the retention time. These attempts include introducing floating dosage forms (gasgenerating systems and swelling or expanding systems), mucoadhesive systems, modified shape
systems, gastric-emptying delaying devices and co-administration of gastric-emptying delaying
drugs. Among these, the floating dosage forms have been used most commonly. However, most
of these approaches are influenced by a number of factors that affect their efficacy as a
gastroretentive system: [18, 19] (Figure 2)
http://www.pharmautility.com
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
modulus
of 48 and 22.5 kilo pounds per square inch (KSI) are reported to have better GRT,
approximately 90% to 100% retention at 24 hours compared with other shapes;
4. Single or multiple unit formulation multiple unit formulations show a more predictable
release profile and insignificant impairing of performance due to
http://www.pharmautility.com
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
containing incompatible
Nature of meal Feeding of indigestible polymers or fatty acid salts can change the
motility pattern of the stomach to a fed state, thus decreasing the gastric emptying
rate and prolonging drug release;
Caloric content GRT can be increased by four to ten hours with a meal that is high in
proteins and fats.
Frequency of feed The GRT can increase by over 400 minutes when successive
meals are given compared with a single meal due to the low
frequency of MMC.
Gender Mean ambulatory GRT in males (3.40.6hours) is less compared with their
age and race matched female counterparts (4.61.2 hours), regardless of the weight,
height and body surface.
Age Elderly people, especially those over 70, have a significantly longer GRT.
Posture GRT can vary between supine and upright ambulatory states of the patient.
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
TECHNOLOGICAL DEVELOPMENTS
Floating systems, first described by Davis [22] in 1986 have bulk density lower than that of the
gastric fluid, and thus remains buoyant in stomach for a prolonged period. While the system is
floating on the gastric components, the drug is released slowly at the desired rate. This results in
increase in the GRT and a better control of fluctuations in the plasma drug concentrations.
Floating systems can be classified into two distinct categories, non-effervescent and effervescent
systems.
A. NON-EFFERVESCENT SYSTEMS
1. Colloidal gel barrier systems
Hydrodynamically balanced system (HBSTM) contain drug with gel forming hydrocolloids
meant to remain buoyant on the stomach contents. This prolongs GI residence time,
maximizes drug reaching its absorption site in the solution form, and hence is ready for
absorption. These systems incorporate high level (20 to 75 % w/w) of one or more gel
forming highly swellable cellulose type hydrocolloids [for eg. Hydroxyethyl cellulose
(HEC), Hydroxypropyl Cellulose (HPC) Hydroxypropyl Methyl Cellulose (HPMC), Sodium
Carboxy Methyl Cellulose (NaCMC) [23], polysaccharides and matrix forming polymers
such as polycarbophill, polyacrylates and polystyrene, incorporated either in tablets or
capsules. On coming in contact with the gastric fluid, the hydrocolloid in the system
hydrates and forms a colloidal gel barrier around its surface. (Figure 3)
http://www.pharmautility.com
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
http://www.pharmautility.com
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
Figure 4
Immediate release layer delivers the initial dose, whereas Sustained Release layer absorbs
gastric fluid and forms a colloidal gel barrier on its surface. This results in system with bulk
density lesser than that of gastric fluid and allows it to remain buoyant in the stomach for an
extended period of time [24].
A multi-layer, flexible, sheath-like device buoyant in gastric juice showing sustained release
characteristics has also been developed [25]. The device consisted of at least one selfsupporting carrier film made up of water insoluble polymer matrix having a drug
dispersed/dissolved therein, and a barrier film overlaying a carrier film. Both carrier and
barrier films were sealed together along their periphery and in such a way as to entrap a
plurality of small air pockets leading to buoyancy of laminated films.
2. Microporous compartment system.
This technology is based on encapsulation of a drug reservoir inside a microporous
compartment with aperture along its top and bottom walls. The peripheral walls of the drug
reservoir compartment are completely sealed to prevent any direct contact of gastric
mucosal surface with undissolved drug. In stomach, the floatation chamber containing
entrapped air causes the delivery system to float over the gastric contents. Gastric fluid
http://www.pharmautility.com
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
enters through the aperture, dissolves the drug, and carries the dissolved drug for continuous
transport across the intestine for absorption. The microporous compartment system is shown
in (Figure 5) [26].
Figure 5
Intragastric floating and sustained release granules of diclofenac sodium were developed
using HPC, Ethyl Cellulose and Calcium silicate as floating carriers, which had a
characteristically porous structure with numerous pores and a large individual pore volume
[26]. The coated granules acquire floating ability from the air trapped in the pores of
Calcium Silicate when they were coated with a polymer.
3. Alginate beads:
Multiunit floating dosage forms have been developed from freeze-dried Calcium alginate
[27]. Spherical beads of approximately 2.5mm in diameter can be prepared by dropping a
Sodium alginate solution in to aqueous solution of Calcium chloride, causing a precipitation
of Calcium alginate. The beads are then separated; snap frozen in liquid nitrogen, and
freeze-dried at - 40oC for 24 hours, leading to formation of porous system, which can
http://www.pharmautility.com
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
maintain floating force for over 12 hrs. When compared with solid beads, which gave a short
residence time of 1 hour, these floating beads gave a prolonged residence time of more than
5.5 hours.
Floating systems comprising of Calcium alginate core separated by an air compartment from
a membrane of Calcium alginate or a Calcium alginate/Polyvinyl Alcohol (PVA) have also
been developed [28]. The porous structure generated by leaching of PVA (water soluble
additive in coating composition) was found to increase membrane permeability, preventing
the collapse of air compartment.
4. Hollow microspheres.
Hollow microspheres (micro balloons), loaded with Ibuprofen in their outer polymer shells
were prepared by novel emulsion solvent diffusion method. The ethanol: dichloromethane
solution of the drug and an enteric acrylic polymer was poured into an agitated aqueous
solution of PVA that was thermally controlled at 40oC. The gas phase generated in dispersed
polymer droplet by evaporation of dichloromethane formed an internal cavity in
microsphere of polymer with drug (Figure 6). The micro balloons floated continuously over
surface of acidic solution media containing surfactant for greater than 12 hours in vitro. The
drug release was high in pH 7.2 than in pH 6.8 [29].
http://www.pharmautility.com
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
antihistamines,
steroids,
antispasmodics,
cardiovascular
http://www.pharmautility.com
preparations,
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
B. Effervescent Systems:
A drug delivery system can be made to float in the stomach by incorporating a floating chamber,
which may be filled with vacuum, air or inert gas. The gas in floating chamber can be introduced
either by volatilization of an organic solvent or by effervescent reaction between organic acids
and bicarbonate salts.
1. Volatile liquid containing systems:
The GRT of a drug delivery system can be sustained by incorporating an inflatable chamber,
which contains a liquid, e.g. Ether, Cyclopentane, that gasifies at body temperature to cause
the inflation of the chamber in the stomach. These devices are osmotically controlled
floating systems containing a hollow deformable unit that can convert from a collapsed to an
expanded position, and returns to collapsed position after an extended period. A deformable
system consists of two chambers separated by an impermeable, pressure responsive,
movable bladder. The first chamber contains the drug and the second chamber contains
volatile liquid. The device inflates, and the drug is continuously released from the reservoir
into the gastric fluid. The device may also consist of bioerodible plug made up of PVA,
Polyethylene, etc. that gradually dissolves causing the inflatable chamber to release gas and
collapse after a predetermined time to permit the spontaneous ejection of the inflatable
system from the stomach (Figure 7) [32].
http://www.pharmautility.com
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
Figure 7
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
delivery orifice. The floating support also contains a bioerodible plug that erodes after a
predetermined time to deflate the support, which is then excreted from the stomach (Figure
8) [33].
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
Multi-unit types of floating pills (Figure 9), which generate CO2, have also been developed
[34]. The system consists of sustained release pill as a seed, surrounded by double layers.
The inner layer is an effervescent layer containing sodium bicarbonate and tartaric acid. The
outer layer is swellable membrane layer. These kinds of systems float completely within 10
minutes, and remain floating over extended period of 5-6 hours [35].
http://www.pharmautility.com
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
EVALUATION OF FDDS
Evaluation of a drug product is a tool to ensure
(1) performance characteristics, and
(2) control batch-to-batch quality,
(3) General appearance, hardness and friability, drug content, weight variation, uniformity of
content, drug release, etc, for gastro retentive performance.
1. Floating time:
The test for buoyancy is usually performed in simulated gastro intestinal fluids maintained at
37 0C. The floating time is determined by using the USP dissolution apparatus containing
900ml of 0.1N HCL as the testing medium maintained at 37 0C. The time for which the
dosage form floats is termed as the floating or floatation time.[36]
2. Specific gravity:
The specific gravity of floating systems can be determined by the displacement method
using benzene as a displacing medium [37].
3. Resultant weight:
Bulk density and floating duration have been the main parameters to describe the adequacy
of dosage forms buoyancy. Resultant weight, corresponds to the vector sum of buoyancy
(Fbuoy) and gravity (Fgrav) forces acting on the object. [38]
F= Fbuoy - Fgrav
F= dfgV-dsgV= (df-ds) gV
F = (df-M/V) gV
Where, 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. By convention, a positive resultant weight signifies force F exerted
http://www.pharmautility.com
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
vertically upwards and that the object is able to float, whereas a negative resultant weight
means that the force F acts vertically downwards and the object sinks (Figure 10). The
crossing of the zero base line by the resultant weight curve from positive towards negative
values indicate transition of the dosage form from floating to non-floating conditions.
Intersection of lines consequently corresponds, on time axis, to the floating time of the
dosage form.
http://www.pharmautility.com
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
http://www.pharmautility.com
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
result in the availability of new products with new therapeutic possibilities and substantial
benefits for patients. Soon, novel gastroretentive products with release and absorption phases of
approximately 24 hrs may replace the so-called once-a-day formulations.
Drugs
Dosage forms
GRT (h)
NFDS*
FDDS
References
Diazepam
Capsules
1-1.5
4-10
[23,38,40]
(Moricizine HCl)
Tablets
1-1.5
>6
[41]
Gentamycin sulfate
Tablets
1-2
>4
[42]
Isradipine
Capsules
0.51-2.87
2.4-4.8
[5]
Metoprolol tartrate
Tablets
1-1.5
5-6
[43]
Miocamycin
Tablets
3-4
>7
[44]
Pepstatin
Minicapsules
NR
3-5
[45]
Salbutamol sulfate
Capsules
NR
8-9
[46]
Tranilast
Microcapsules
NR
>3
[4]
http://www.pharmautility.com
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
REFERENCES
[1]
N. Rouge, P. Buri, E. Doelker, Drug absorption sites in the gastrointestinal tract and
dosage forms for site-specific delivery, Int. J. Pharm. 136 (1996) 117139.
[2]
S. Desai, A novel floating controlled release drug delivery system based on a dried gel
matrix, M.S. thesis, St. Johns University, Jamaica, NY, 1984.
[3]
J.T. Fell, Targeting of drugs and delivery systems to specific sites in the gastrointestinal
tract, J. Anat. 189 (1996) 517 519.
[4]
J.A. Fix, R. Cargill, K. Engle, Controlled gastric emptying.III. Gastric residence time of a
nondisintegrating geometric shape in human volunteers, Pharm. Res. 10 (1993) 1087
1089.
[5]
[6]
A. Rubinstein, D.R. Friend, Specific delivery to the gastroin-testinal tract, in: A.J. Domb
(Ed.), Polymeric Site-Specific Pharmacotherapy, Wiley, Chichester, 1994, pp. 282283.
[7]
[8]
[9]
M. Oth, M. Franz, J. Timmermans, A. Moes, The bilayer floating capsule: a stomachdirected drug delivery system for misoprostol, Pharm. Res. 9 (1992) 298302.
[10]
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
[11]
www.aventis-us.com.
[12]
[13]
J. Timmermans, A.J. Moes, Factors controlling the buoyancy and gastric retention
capabilities of floating matrix capsules: new data for reconsidering the controversy, J.
Pharm. Sci. 83(1994) 1824.
[14]
[15]
M.J. Blaser, Hypotheses on the pathogenesis and natural history of Helicobacter pyloriinduced inflammation, Gastroenterology 102 (1992) 720727.
[16]
[17]
[18]
P. Mojaverian, P.H. Vlasses, P.E. Kellner, M.L. Rocci Jr., Effects of gender, posture, and
age on gastric residence time of an indigestible solid: pharmaceutical considerations,
Pharm. Res. 10 (1988) 639644.
[19]
J. Timmermans, A.J. Moes, How well do floating dosage forms float?, Int. J. Pharm. 62
(1990) 207216.
[20]
Jerome Besse, Listrac Medoc, Gastric retained pharmaceutical composition and methods
for its use, US Patent Pub. No. US 2001/0046473 A1,Nov. 29, 2001.
[21]
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
[22]
S.S. Davis, A.F. Stockwell, M.J. Taylor, J.G. Hardy, D.R. Whalley, C.G. Wilson, H.
Bechgaard, F.N. Christensen, The effect of density on the gastric emptying of single- and
multiple-unit dosage forms, Pharm. Res. 3 (1986) 208213.
[23]
P.R. Sheth, J. Tossounian, The hydrodynamically balanced system (HBSE): a novel drug
delivery system for oral use, Drug Dev. Ind. Pharm. 10 (1984) 313339.
[24]
A.K. Hilton, P.B. Deasy, In vitro and in vivo evaluation of an oral sustained-release
floating dosage form of amoxycillin trihydrate, Int. J. Pharm. 86 (1992) 7988.
[25]
S.B. Mitra, Sustained release oral medicinal delivery device, US Patent 4, 451, 260, May
29, 1984.
[26]
Roy. Harrigan. M, Drug Delivery device for preventing contact of undissolved drug with
stomach lining. U.S.Patent No. 4055178. March 10, 1976.
[27]
[28]
L. Whitehead, J.T. Fell, J.H. Collett, H.L. Sharma, A.-M. Smith, Floating dosage forms:
an in vivo study demonstrating prolonged gastric retention, J. Control. Release 55 (1998)
312.
[29]
[30]
[31]
Sanford Bolton and Subhash Desai, Floating sustained release therapeutic compositions,
US Patent 4,814,179, March 21, 1989.
[32]
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
release characteristics (in vitro) and floating behavior (in vivo) J. Control. Release 16
(1991) 279290.
[33]
A.S. Michaels, J.D. Bashwa, A. Zaffaroni, Integrated device for administering beneficial
drug at programmed rate, US Patent 3, 901, 232, August 26, 1975.
[34]
A.S. Michaels, Drug delivery device with self actuated mechanism for retaining device in
selected area, US Patent 3, 786, 813, January 22, 1974.
[35]
[36]
[37]
[38]
[39]
[40]
J.H. Gustafson, L. Weissman, R.E. Weinfeld, A.A. Holazo,K.-C. Khoo, S.A. Kaplan,
Clinical bioavailability evaluation of a controlled release formulation of diazepam, J.
Pharmacokinet. Biopharm. 9 (1981) 679691.
http://www.pharmautility.com
ISSN: 2319-5894
Pharma Utility Volume 7, Issue 1, 2013
[41]
B.M. Regmi, J.P. Liu, X.D. Tu, Studies on ethmozine (EMZ)Sustained release tablets,
remaining-floating in stomach, Yao Hsueh Hsueh Pao 31 (1996) 5458, Abstract in
English, Article in Chinese.
[42]
W.L. Xu, X.D. Tu, Z.D. Lu, Development of gentamicin sulfate sustained-release tablets
remaining-floating in stomach, Yao Hsueh Hsueh Pao 26 (1991) 541545, Abstract in
English, Article in Chinese.
[43]
S.L. Li, X.D. Tu, F.F. Mao, Development and pharmacokinetic study of metoprolol
tartrate controlled-release remaining-floating in stomach, Yao Hsueh Hsueh Pao 24
(1989) 381386, Abstract in English, Article in Chinese.
[44]
Y. Diao, X.D. Tu, Development and pharmacokinetic study of miocamycin sustainedrelease tablets remaining-floating in stomach, Yao Hsueh Hsueh Pao 26 (1991) 695700,
Abstract in English, Article in Chinese
[45]
H. Umezawa, Pepstatin floating minicapsules, US Patent 4, 101, 650, July 18, 1978.
[46]
V.B.M. Babu, R.K. Khar, In vitro and in vivo studies of sustained-release floating dosage
forms containing salbutamol sulfate, Pharmazie 45 (1990) 268270.
[47]
N. K. Jain, Progress in controlled and Novel drug delivery, First edition ,CBS publishers,
New Delhi, (2001), 76-95.
[48]
B.M. Singh and K. H. Kim, Floating drug delivery system; An approach to controlled
drug delivery via gastric retention, J. Control. Release, 63 (2000), 235-259.
http://www.pharmautility.com