Download Oral Extended Release Drug Delivery System: A Promising Approach

[AJPTech.]
Asian J. Pharm. Tech. 2012; Vol. 2: Issue 2, Pg 38-43
ISSN- 2231–5705 (Print)
www.asianpharmaonline.org
ISSN- 2231–5713 (Online) 0974-3618
REVIEW ARTICLE
Oral Extended Release Drug Delivery System: A Promising Approach
Sunil Kumar1, Anil Kumar1, Vaibhav Gupta1, Kuldeep Malodia1 and Pankaj Rakha2
1
Lord Shiva College of Pharmacy, Sirsa, Haryana( India).
Shri Baba Mastnath Institute of Pharmaceutical Sciences and Research, Asthal Bohr, Rohtak,
Haryana (India).
*Corresponding Author E-mail: [email protected]
2
ABSTRACT:
Oral drug delivery is the most preferred route for the various drug molecules among all other routes of drug delivery,
because ease of administration which lead to better patient compliance. So, oral extended release drug delivery system
becomes a very promising approach for those drugs that are given orally but having the shorter half-life and high dosing
frequency. Extended release drug delivery system which reduce the dosing frequency of certain drugs by releasing the
drug slowly over an extended period of time. There are various physiochemical and biological properties which affect
the extended release drug delivery system. This article providing the recent literature regarding development and design
of extended release tablets.
KEY WORDS: Extended Release, Extended Release Drug Delivery System, Half Life.
INTRODUCTION:
Oral route is the most oldest and convenient route for the
administration of therapeutic agents because of low cost of
therapy and ease of administration leads to higher level of
patient compliance.1 Approximately 50% of the drug
delivery systems available in the market are oral drug
delivery systems and historically too, oral drug
administration has been the predominant route for drug
delivery.2,3 It does not pose the sterility problem and
minimal risk of damage at the site of administration.4
The sustained release, sustained action, prolonged action,
controlled release, extended action, timed release, depot and
respiratory dosage forms are terms used to identify drug
delivery system that are designed to achieve a prolonged
therapeutic effect by continuously releasing medication
over an extended period of time after administration of a
single dose
Extended release formulation is an important program for
new drug research and development to meet several unmet
clinical needs. There are several reasons for attractiveness
of these dosage forms viz. provides increase bioavailability
of drug product, reduction in the frequency of
administration to prolong duration of effective blood levels,
Reduces the fluctuation of peak trough concentration and
side effects and possibly improves the specific distribution
of the drug.9
During the past three decades, numerous oral delivery
systems have been developed to act as drug reservoirs from
which the active substance can be released over a defined
period of time at a predetermined and controlled rate.5 The
oral controlled release formulation have been developed for
those drug that are easily absorbed from the gastrointestinal
tract (GIT) and have a short half-life are eliminated quickly
from the blood circulation.6 As these will release the drug
slowly into the GIT and maintain a constant drug Extended release drug delivery system achieves a slow
release of the drug over an extended period of time or the
concentration in the plasma for a longer period of time.7
drug is absorbed over a longer period of time. Extended
release dosage form initially releases an adequate amount of
drug to bring about the necessary blood concentration
(loading dose, DL) for the desired therapeutic response and
therefore, further amount of drug is released at a controlled
rate (maintenance dose, DM) to maintain the said blood
levels for some desirable period of time.10,11
Received on 11.05.2012
Accepted on 24.05.2012
© Asian Pharma Press All Right Reserved
Asian J. Pharm. Tech. 2(2): April-June 2012; Page 38-43
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[AJPTech.]
Asian J. Pharm. Tech. 2012; Vol. 2: Issue 2, Pg 38-43
time of undissolved drug and limited solubility at
absorption site. So these types of drug are undesirable to be
formulated as extended release drug delivery system. Drug
having extreme aqueous solubility are undesirable for
extended release because, it is too difficult to control release
Suitable Drug Candidate for Extended Release Drug of drug from the dosage form.
Delivery System:
The drugs that have to be formulated as a ERDDS should Partition Co-efficient:
meet following parameters.
As biological membrane is lipophilic in nature through
•
It should be orally effective and stable in GIT medium. which the drug has to pass, so partition co-efficient of drug
•
Drugs that have short half-life, ideally a drug with half influence the bioavailability of drug very much. Drug
life in the range of 2 – 4 hrs makes a good candidate for having lower partition co-efficient values less than the
formulation into ER dosage forms eg. Captopril, optimum activity are undesirable for oral ER drug delivery
system, as it will have very less lipid solubility and the drug
Salbutamol sulphate.
•
The dose of the drug should be less than 0.5g as the will be localized at the first aqueous phase it come in
oral route is suitable for drugs given in dose as high as 1.0g contact. Drug having higher partition co-efficient value
greater than the optimum activity are undesirable for oral
eg. Metronidazole.
•
Therapeutic range of the drug must be high. A drug for ER drug delivery system because more lipid soluble drug
ERDDS should have therapeutic range wide enough such will not partition out of the lipid membrane once it gets in
that variations in the release do not result in concentration the membrane.
beyond the minimum toxic levels14
Protein Binding:
The Pharmacological response of drug depends on unbound
Merits of Extended Release Drug Delivery System:
•
The extended release formulations may maintain drug concentration rather than total concentration and all
drugs bound to some extent to plasma and/or tissue
therapeutic concentrations over prolonged periods.
•
The use of extended release formulations avoids the proteins. Proteins binding of drug play a significant role in
its therapeutic effect regardless the type of dosage form as
high blood concentration.
extensive binding to plasma, increase biological half life
•
Reduce the toxicity by slowing drug absorption.
and thus, such type of drug will release upto extended
•
Minimize the local and systemic side effects.
period of time then there is no need to develop extended
•
Improvement in treatment efficacy.
release drug delivery for this type of drug.
•
Minimize drug accumulation with chronic dosing.
•
Improvement of the ability to provide special effects.
•
Enhancement of activity duration for short half life Drug Stability:
As most of ER Drug delivery system is designing to release
drugs.
drug over the length of the GIT, hence drug should be
stable in GI environment. So drug, which is unstable, can’t
Demerits Extended Release Drug Delivery System:
Despite of several merits, extended release dosage forms be formulated as oral ER drug delivery system, because of
bioavailability problem.
are not devoid of certain demerits explained following:
•
In case of acute toxicity, prompt termination of therapy
Mechanism and Site of Absorption:
is not possible.
•
Less flexibility in adjusting doses and dosage Drug absorption by carrier mediated transport and those
absorbed through a window are poor candidate for oral ER
regimens.
•
Risk of dose dumping upon fast release of contained drug delivery system. Drugs absorbed by passive diffusion,
pore transport and through over the entire length of GIT are
drug.
suitable candidates for oral ER drug delivery system.
•
High cost of preparation.
•
The release rates are affected by various factors such
Dose Size:
as, food and the rate transit through the gut.
•
The larger size of extended release products may cause If a product has dose size >0.5g it is a poor candidate for
ER drug delivery system, because increase in bulk of the
difficulties in ingestion or transit through gut.15,16,17
drug, thus increases the volume of the product. Thus dose
Factors Affecting the Extended Release Drug Delivery of drug should small to make a good drug candidate for
extended release drug delivery system.
System:
Objectives of Extended Release Drug Delivery System:
Every noval drug delivery system had a rationale for
developing the dosage form likewise, ERDDS also having
some objectives that are discussed below: :
Physiochemical Properties:
Aqueous Solubility:
Certain drug substance having low solubility is reported to
be 0.1 mg/mL. As the drug must be in solution form before
absorption, drug having low aqueous solubility usually
suffers oral bioavailability problem due to limited GI transit
Biological Properties:
Absorption:
The absorption behaviour of a drug can affect its suitability
as an extended release product. The aim of formulating an
extended release product is to place a control on the
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delivery system. It is essential that the rate of release is
much slower than the rate of absorption. If we assume the
transit time of most drugs and devices in the absorptive
areas of GI tract is about 8-12 hours, the maximum half-life
for absorption should be approximately 3-4 hours.
Otherwise the device will pass out of absorptive regions
before drug release is complete. Therefore the compounds
with lower absorption rate constants are poor candidates for
extended release systems. Some possible reasons for a low
extent of absorption are poor water solubility, small
partition co-efficient, acid hydrolysis, and metabolism or its
site of absorption.
dispersed in an insoluble matrix of rigid non swellable
hydrophobic matrials is called as matrix system. Materials
used for rigid matrix are insoluble plastics such as PVC and
fatty materials like stearic acid, beewax etc. With plastic
materials the drug is generally kneaded with the solution of
PVC in an organic solvent and granulated. It is a hollow
system containing an inner drug core surrounded in water
insoluble membrane is called as reservoir devices. Polymer
can be applied by coating or microencapsulation. The rate
controlling mechanism partitioning into membrane with
subsequent release into surrounding fluid by diffusion and
commonly used polymers are HPC, EC and PVA.
Distribution:
The distribution of drugs in tissues can be important factor
in the overall drug elimination kinetics. Since it not only
lowers the concentration of circulating drug but it also can
be rate limiting in its equilibrium with blood and extra
vascular tissue, consequently apparent volume of
distribution assumes different values depending on time
course of drug disposition. Drugs with high apparent
volume of distribution, which influence the rate of
elimination of the drug, are poor candidate for oral ER drug
delivery system e.g. Chloroquine. For design of extended
release products, one must have information on disposition
of the drug.
Dissolution Controlled Drug Release:
In these products, the rate dissolution of the drug (and
thereby availability for absorption) is controlled by slowly
soluble polymer or by microencapsulation. Once the
coating is dissolved, the drug becomes available for
dissolution. By varying the thicknesses of the coat and its
composition, the release rate of drug can be controlled.
These systems are easiest to design. With inherently slow
dissolution rate. Such drugs act as a natural prolonged
release products. That produces slow dissolving forms
when it comes in contact with GI fluids and having high
aqueous solubility and dissolution rate.
Metabolism:
Drug, which extensively metabolized is not suitable for ER
drug delivery system. A drug capable of inducing
metabolism, inhibiting metabolism, metabolized at the site
of absorption or first-pass effect is poor candidate for ER
delivery, since it could be difficult to maintain constant
blood level e.g. levodopa, nitroglycerine. Drugs that are
metabolised before absorption, either in lumen or the tissues
of the intestine, can show decreased bioavailability from the
extended releasing systems. Most intestinal walls are
saturated with enzymes. As drug is released at a slow rate to
these regions, lesser drug is available in the enzyme system.
Hence the systems should be devised so that the drug
remains in that environment to allow more complete
conversion of the drug to its metabolite.
Osmotically Controlled Drug Release:
The rate of release of drug in these products is determined
by the constant in flow of water across a semi permeable
membrane into a reservoir which contains an osmotic agent
called as osmogens. The rate of release is constant and can
be controlled within tight limits yielding relatively constant
blood concentration. The advantage of this type of product
is that the constant release is unaltered by the environment
of the gastrointestinal tract and relies simply on the passage
of water into the dosage form. The rate of release can be
modified by altering the osmotic agent and the size of the
hole.
Half-life of Drug:
A drug having biological half-life between 2 to 8 hours is
best suited for oral ER drug delivery system. As if
biological half-life < 2hrs the system will require
unacceptably large rate and large dose and biological halflife > 8hrs formulation of such drug into ER drug delivery
system is unnecessary.16,18-20
Swelling Controlled Drug Release System:
It is useful for sustaining the release of highly soluble drug.
The materials for such matrices are hydrophilic gums and
natural origin (guar gum, tragacanth), semi-synthetic
(HPMC,
CMC,
Xanthan
gum)
or
synthetic
(Polyacrylamides). The drug and gum are granulated
together with solvent such as alcohol and compressed into
tablets. The release of drug from initially dehydrated hydro
gels involves adsorption of water and desorption of drug
from a swelling controlled diffusion system. As the gum
swell and the drug diffuses out of it.
Mechanistic Aspects of Oral Extended Release System
Continuous Releases:
Diffusion Controlled Drug Release:
In this system the rate controlling step is not the dissolution
rate but the diffusion of dissolved drug through a polymeric
barrier. The two types of diffusion controlled system are –
Matrix System and Reservoir Devices. The drug is
Chemically Controlled Drug Release:
In this system the drug is chemically bound to a matrix
(which is not necessarily biodegradable), coated solid
dosage forms from which drug release occurs only upon
crack formation within the surrounding membrane, and
microchip-based drug delivery systems. If the drug is
covalently bound to an insoluble matrix former via
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hydrolysable bondings, the latter are more or less rapidly drug particles use of mucoadhesive polymer and altering
the size of the dosage form.
cleaved upon water penetration into the device.
Dissolution and Diffusion Controlled Release System:
In this system the drug core is encased in a partially soluble
membrane. Pores are thus created due to dissolution of parts
of membrane which permits entry of aqueous medium into
the drug core and hence drug dissolution allows diffusion of
dissolved drug out of the system. An example of obtaining
such a coating is using a mixture of ethyl cellulose with
PVP or methyl cellulose; the latter dissolves in water and
creates pores in the insoluble ethyl cellulose membrane.
Mucoadhesive System:
A bioadhesive polymer such as cross-linked polyacrylic
acid, when incorporated in a tablet, allows it to adhere to
the gastric mucosa or epithelium. Such a system
continuously releases a fraction of drug into the intestine
over prolonged periods of time.
Size-Based System:
Gastric emptying of a dosage form can be delayed in the fed
state if its size is greater than 2 mm. Dosage form of size
2.5 cm or larger is often required to delay emptying long
Hydrodynamic Pressure Controlled Release System:
A hydrodynamic pressure-activated drug delivery system enough to allow once daily dosing. Such forms are however
can be fabricated by enclosing a collapsible, impermeable to swallow.
container, which contains a liquid drug formulation to form
a dug reservoir compartment, inside rigid shape retaining Delayed Release System:
housing. A composite laminate of an absorbent layer and Intestinal Release System:
swellable, hydrophilic polymer layer is sandwiched A drug may be enteric coated for intestinal release for
between the drug reservoir compartment and the housing. In several known reasons such as to prevent gastric irritation,
the GI tract the laminate absorb the gastrointestinal fluid prevent destabilization in gastric pH, etc. Certain drugs are
through the annular opening at the lower end of the housing delivered to the distal end of small intestine for absorption
and become increasingly swollen, which generates via peyer’s patches or lymphatic system. Peyer’s patches
hydrodynamic pressure in the system. The hydrodynamic are mucosal lymphoid tissues that are known to absorb
pressure thus created forces the drug reservoir compartment macromolecules like proteins and peptides and antigens by
to reduce in volume and causes the liquid drug formulation endocytosis. Selective release of such agents to peyer’s
to release through the delivery orifice at the specific rate21. patch region prevents them from getting destroyed/digested
by the intestinal enzymes. Such a site can be utilized for
Such systems are also called as push-pull osmotic pumps.
oral delivery of insulin.
pH-Independent Formulation:
Such system are designed to eliminate the influence of Colonic Release System:
changing the gastrointestinal pH on dissolution and Drugs are poorly absorbed through colon but may be
absorption of drugs by formulating them with sufficient delivered to such a site for two reasons – Local actions as in
amount of buffering agents (salts of phosphoric, citric or the treatment of ulcerative colitis with mesalamine and
tartaric acids) that adjust the pH to the desired value as the systemic absorption of protein and peptide drugs like
dosage form passes along the GIT and permit drug insulin and vasopressin. The advantage is taken of the fact
pH
sensitive
bioerodible
polymers
like
dissolution and release at a constant rate independent of that
gastrointestinal pH. The dosage form containing drug and polymethacrylates release the medicament only at the
buffer is coated with a permeable substance that allows alkaline pH of colon or use of divinylbenzene cross-linked
entry of aqueous medium but prevents dispersion of tablets. polymer that can be cleaved only by the azoreductase of
colonic bacteria to release free drug for local effect or
systemic absorption.21,22
Delayed Transit and Continuous Release System:
These systems are designed to prolong their residence in the
GIT along with their release. Often, the dosage form is Polymers Used in Preparations of CRDDS
fabricated to detain in the stomach and hence the drug Hydrogels:
present therein should be stable to gastric pH. Systems • Polyhydroxyethylmethylacrylate (PHEMA)
included in this category are as follows:
•
Cross-linked polyvinyl alcohol (PVA)
•
Cross-linked polyvinylpyrrolidone (PVP)
Altered Density System:
•
Polyethyleneoxide (PEO)
The transit time of GI contents is usually less than 24 hours. • Polyacrylamide (PA)
This is the major limiting factor in the design of oral
controlled release formulation which can reduce the Soluble Polymers:
frequency of dosing to a time period little more than the • Polyethyleneglycol (PEG)
residence time of drug. If the residence time of drug in the • Polyvinyl alcohol (PVA)
stomach or intestine is prolonged in some way the • Polyvinylpyrrolidone (PVP)
frequency of dosing can be reduced. There are 3 ways by • Hydroxypropylmethylcellulose (HPMC)
which this can be achieved such as altering the density of
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Table 1: Extended Release Tablets Available in National and International Market
Brand Name
Active Ingredient(s)
Metapure-XL Tab
Metoprolol Succinate
Etomax – ER Tab
Etodolac
Betacap –TR Cap
Propranolol HCl
Metaride Tab
Glimipiride and Metformin HCl
Augmentin – XR Tab
Amixicillin and Potassium Clavulanate
Wellbutrin - XL Tab
Buproprion HCl
Revelol – XL Tab
Metoprolol Succinate
Dayo – OD Tab
Divolproex Sodium
Sentosa – ER Tab
Venlafaxine
Zanocin – OD Tab
Ofloxacin
Glizid – MR Tab
Gliclazide
Metzok Tab
Metoprolol Succinate
Tegritol - CR Tab
Carbemezapine
Glimestar PM Tab
Glimipride,Pioglitazone and metformin
Supermet – XL Tab
Metoprolol Succinate
Gabaneuron – SR Tab
Gabapentin and Methylcobalamin
Cefoclox – XL Tab
Cefpodoxime Dicloxacillin and Lactic acid bacillus
Zen Retard Tab
Carbemezapine
Tolol AM Tab
Metoprolol Succinate
Exermet GM 502 Tab
Glimepiride and Metformin HCl
Mahacef – XL Tab
Cefpodoxime Dicloxacillin and Lactic acid bacillus
Gluconorm PG Tab
Glimepiride, Pioglitazone and Metformin HCl
Minipress –XL Tab
Parazocin HCl
Pomed – EX Tab
Pantaprozol and domperidone
Riomet – Trio 2 Tab
Metformin HCl
Divaa – OD Tab
Divalproex Sodium
Metocontin Tab
Metoclopramide HCl
Fecontin – F Tab
Ferrous Glycine Sulphate and Folic acid
Diucontin – K 20/250 Tab
Frusemide
Unicontin – E Tab
Theophyllin
Licab – XL Tab
Lithium Carbonate
Embeta – XR Tab
Metoprolol Succinate
Glycomet – 1 GM Tab
Metformin HCl
Venlor – XR Tab
Venlafexine HCl
Altiva – D Tab
Fexofenadine HCl and Pseudoephidrine sulphate
Sporidex – AF Tab
Cefalaxin
Vasovin- XL Tab
Nitroglycerin
Lithosun SR Tab
Lithium Carbonate
Etura Tab
Etodolac
Intalith CR
Lithium Carbonate
Pari – SR Tab
Proxitine HCl
Reolol – AM 25/5 Tab
Metoprolol Succinate
Valprol – CR Tab
Metoprolol Succinate and Amlodipine
Perinorm – CD Cap
Sodium Valproate and Valproic Acid
Gluconorm G Tab
Metformin HCl
Zetpol CR Tab
Carbemezapine
Epsolin ER Cap
Phenytoin Sodium
Gluconorm – SR Tab
Metformin HCl
Carvidon – MR Tab
Trimetazidine HCl
Biodegradeble Polymers:
•
Polylactic acid (PLA)
•
Polyglycolic acid (PGA)
•
Polycaprolactone (PLA)
•
Polyanhydrides
•
Polyorthoesters
Manufacturer
Emcure, Mumbai
Ipca, Mumbai
Sun Pharma, J and K
Unichem, Mumbai
Glaxosmithkline, Mumbai
Glaxosmithkline, Mumbai
Ipca, Mumbai
Lupin, Baddi(HP)
Nicholas Piramal, Baddi(HP)
Ranbaxy, Ponta Sahib.
Panacea Biotech, Lalru(CHD).
USV, Mumbai
Novartis, Goa
Discovery Mankind, Ponta Sahib
Piramal Healthcare, Baddi(HP)
Aristo, Baddi(HP)
Khandelwal
Intas, Ahemdabad
Unichem, Mumbai
Cipla, Baddi(HP)
Discovery Mankind, Ponta Sahib
Lupin, Baddi (HP)
Pfizer, Goa
Panjon
Ranbaxy, Ponta Sahib
Intas, Ahemdabad
Modi-Mundi Pharma, Meerut
Modi-Mundi Pharma, Meerut
Modi-Mundi Pharma, Meerut
Modi-Mundi Pharma, Meerut
Torrent, Ahemdabad
Intas, Ahemdabad
USV, Mumbai
Cipla Protec, Baddi(HP)
Sidmak
Ranbaxy, Ponta Sahib
Torrent, Ahemdabad
Sun Pharma, J and K
Dr’ Reddy, Hydrabad
Intas, Ahmadabad
Ipca, Mumbai
Ipca, Mumbai
Intas, Ahmadabad
Ipca, Mumbai
Lupin, Baddi(HP)
Sun Pharma, J and K
Zydus, Ahmadabad
Lupin, Baddi(HP)
Microlab, Banglore
Non Biodegradeble Polymers:
•
Polyethylene vinyl acetate (PVA)
•
Polydimethylsiloxane (PDS)
•
Polyetherurethane (PEU)
•
Polyvinyl chloride (PVC)
•
Cellulose acetate (CA)
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Mucoadhesive Polymers :
•
Polycarbophil
•
Sodium carboxymethyl cellulose
•
Polyacrilic acid
•
Tragacanth
•
Methyl cellulose
•
Pectin
•
Natural gums
•
Xanthan gum
•
Guar gum
•
Karaya gum23
9.
10.
11.
12.
Extended Release Tablets Available in National and
International Markets:
13.
There are so many ER Tablets of different drug molecule by
different manufacturers are available in the market. Some of
14.
their name is depicted in table 1.
CONCLUSION:
15.
We concluded from the above discussion that extended
release formulations are very much helpful in increasing the
effectiveness of the drugs with short half life and also
improve patient compliance by decreasing the dosing
frequency. Now, a wide range of drugs are formulated in a
variety of different oral extended release dosage forms.
However, only those which result in a significant reduction
in dose frequency and a reduction in toxicity resulting from
high concentration in the blood or gastrointestinal tract are
likely to improve therapeutic outcomes. To be a successful
extended release product, the drug must be released from
the dosage form at a predetermined rate, dissolve in the
gastrointestinal fluids, maintain sufficient gastrointestinal
residence time, and may be absorbed at a rate and will
replace the amount of drug being metabolized and excreted.
16.
17.
18.
19.
20.
21.
22.
REFERENCES:
1.
2.
3.
4.
5.
6.
7.
8.
Aher K B, Bhavar G B, Joshi H P, Chaudhari S R, Recent
advances in compression-coated tablets as a controlled drug
delivery system, Saudi pharmaceutical journal, 2011, 01.
Shivakumar H G, Gowda D V, Kumar T M P, Floating controlled
drug delivery systems for prolonged gastric residence: a review,
Ind. J. Pharm., 2004, 38(45), 172-78.
Sharma A, Sharma S, Jha K K, The study of salbutamol matrix
tablets using different polymers as release retarding agent, The
pharma research, 2009, 01, 15-22.
Sharma P P, Sharma S, Khokra S L, Sahu R K, Jangde R, Singh
J, Formulation, development and evaluation of sustained release
matrix
tablets
containing
salbutamol
sulphate,
Pharmacologyonline2, 2011, 1197-1203.
Chein Y W, Oral drug delivery and delivery systems, Marcel
dekker,inc.,New York, 1992, 01, 139-96.
Ahsan M Q, Rahman M M, Jha M K, Ahmed I, Moghal M M R,
Rahman M H, Development and in-vitro evaluation of sustained
release matrix tablets of salbutamol sulphate using methocel
K100M CR polymer, International journal of pharmaceutical
sciences and research, 2011, 02(03), 567-76.
Modi S A, Gaikwad P D, Bankar V H, Pawar S P, Sustained
release drug delivery system: A review, International journal of
pharma. Research and development, 2011, 02(12), 147-59.
Murthy P N V N, Shafiullah D, Datta M, Formulation,
development and evaluation of controlled release matrix tablets
23.
43
of guaiphenesin and salbutamol sulphate, Der pharmacia letter,
2011, 3(4), 325-334.
El-halim S M A, Amin M M, Gazayerly O N E, Gawad N A A E,
Salbutamol sulphate controlled release hydrophllic matrix tablets,
RGUHS journal of pharmaceutical sciences, 2011, 01(03), 194200.
Khan M G, Controlled release oral dosage forms: Some recent
advances in matrix type drug delivery systems, The sciences,
2001, 1(5), 350-354.
Ghosh A, Gupta K S, Formulation, development and in-vitro
evaluation of sustained release matrix tablets of salbutamol
sulphate, JPRHC, 2003, 02(03),222-27.
Srivastav M, Prabhakar, Omray A, Extended release tablet
technologies-matrix, melt granulation and multiparticulates: An
overview, International journal of universal pharmacy and life
sciences, 2011, 01(02), 331-54.
Ratial D A, Gaikwad P D, Bankar V H, Pawar S P, A review on:
Sustained released technology, International journal of research
in ayurveda and pharmacy, 2011, 02(06), 1701-08.
Jayanthi B, Manna P M, Madhusudhan S, Mohanta G P,
Manavalan R, Per oral extended release products- A overview,
Journal of applied pharmaceutical science, 2011, 01(02), 50-55.
Pogula M, Nazeer S, Extended release formulation, International
journal of pharmacy and technology, 2010, 02(04), 625-84.
Jain N K, Controlled and novel drug delivery system, In progress
in controlled and novel drug delivery system, C B S publishers
and distributors, New delhi, 2004, 01. 419-35.
Dandagi P M, Masthiholimath V S, Patil M B, Manvi F V, Gadad
A P, Sharma R, Development and evaluation of theophylline and
salbutamol sulphate sustained release matrix tablets, Indian
journal of pharm. Sci.,2005, 76(05), 598-602.
Brahmankar D M, Jaiswal S B, A treatise of biopharmaceutics
and pharmacokinetics, Vallabh Prakashan, 1995, 01, 335-55.
Maderuelo C, Zarzuelo A, Lanao, Critical factors in the release of
drugs from sustained release hydrophilic matrices, journal of
controlled release, 2011, 154, 2-19.
Banker S G, Rhodes C T, Modern pharmaceutics, Sustained and
controlled release drug delivery systems, 2005, 01, 501-13.
Robinson J R, Lee V H L, Controlled drug delivery
“Fundamentals and application”, Informa Healthcare, 2009, 20,
373-421.
Verma R K, Krishna D M, Garg S, Formulation aspects in the
development of osmotically controlled oral drug delivery
systems, Journal of Controlled Release, 2002, 79, 7-27.
Raizada A, Bandari A, Kumar B, Polymers in drug delivery: A
review, International Journal of Pharma. Research and
Development, 2010, 02(08), 9-20.