JOSR: Journal of Social Research

Desember 2022, 2 (1), 126-133

p-ISSN: 2827-9832 e-ISSN: 2828-335x

Available online at http:// https://ijsr.internationaljournallabs.com/index.php/ijsr

http://ijsr.internationaljournallabs.com/index.php/ijsr

Literature Review Article: Drug Delivery System held in the Stomach

(gastroretentive)

Nurhalifah, Prayoga Daffa Sundawan, Santika Citra Veronita, Shella Imka Puji

Destria, Siti Nuryamah, Nia Yuniarsih

Faculty of Pharmacy, Buana Perjuangan Karawang University

fm19.nurhalifah@mhs.ubpkarawang.ac.id, fm19.prayogasundawan@mhs.ubpkarawang.ac.id,

fm19.santikaveronita@mhs.ubpkarawang.ac.id, fm19.shelladestria@mhs.ubpkarawang.ac.id,

fm19.sitinuryamah@mhs.ubpkarawang.ac.id, nia.yuniarsih@ubpkarawang.ac.id

Abstract (Indonesia)

Received:

Revised :

Accepted:

November 29,

2022

Desember 01,

2022

Desember 03,

2022

Latar Belakang: Obat merupakan suatu subtansi yang

melalui efek kimianya membawa perubahan dalam fungsi

biologi. Sistem penghantaran GRDDS merupakan suatu

system penghantaran obat tertunda (sustained) yang dapat

menahan obat agar berada di dalam lambung dalam waktu

yang lebih lama. Keuntungan dari GRDDS antara lain dapat

meningkatkan bioavailabilitas, meningkatkan kelarutan obat

yang kurang larut dalam pH tinggi, dapat mengontrol level

terapi sehingga mengurangi terjadinya fluktuasi, dapat

memperpanjang waktu paruh sehingga frekuensi pemberian

obat dapat dikurangi.

Tujuan: Penelitian ini betujuan untuk menguraikan tipe-tipe

sediaan GRDDS. Variasi tersebut disebabkan adanya

kombinasi dari perbedaan mekanisme dan teknologinya.

Metode: Rancangan dalam penelitian ini menggunakan

systematic review tinjauan litelatur review yang

mengidentifikasikan, menilai dan menginterprestasi seluruh

temuan-temuan pada suatu topik penelitian.

Hasilnya: Sistem floating dapat menggunakan bahan

polimer yang dapat mengembang seperti HPMC dan

chitosan. Mekanisme floating diawali dengan adanya kontak

cairan lambung dengan tablet yang menyebabkan polimer

mengalami hidrasi membentuk lapisan gel yang dapat

menahan gas CO2 yang terbentuk akibat interaksi natrium

bikarbonat dengan asam sitrat sehingga tablet dapat

mengembang dan dapat mengapung. Rute penghantaran obat

oral merupakan rute yang paling banyak disukai karena

mudah untuk digunakan. Absorpsi obat oral sebagian besar

terjadi di lambung dan di usus.

Kesimpulan: Maka dari itu, perlu adanya sistem

penghantaran obat yang dapat memperpanjang waktu kontak

Nurhalifah, Prayoga Daffa Sundawan, Santika Citra Veronita, Shella Imka Puji Destria, Siti

Nuryamah, Nia Yuniarsih / JOSR: Journal of Social Research, 2(1), 126-133

Literature Review Article: Drug Delivery System Held in the Stomach

(Gastroretentive) 127

dengan lambung, yakni Gastroretentive Drug Delivery

System (GRDDS).

Keywords: obat, GRDDS, system floating

Abstract (English)

Background: Medicine is a substance that through its

chemical effects brings about changes in biological

functions. The GRDDS delivery system is a sustained drug

delivery system that can hold drugs back in the stomach for

a longer time. The advantages of GRDDS include being

able to increase bioavailability, increase the solubility of

drugs that are poorly soluble in high pH, can control of

therapeutic levels to reduce the occurrence of fluctuations,

can extend the half-life so that the frequency of drug

administration can be reduced.

Objectives: This study aims to describe the types of GRDDS

preparations. The variation is due to a combination of

differences in mechanisms and technology.

Method: The design in this study uses a systematic review

of the review process that identifies, assesses, and interprets

all findings on a research topic.

Result: Floating systems can use expandable polymeric

materials such as HPMC and chitosan. The floating

mechanism begins with the contact of gastric juices with

tablets which causes the polymer to hydrate to form a gel

layer that can withstand CO2 gas formed due to the

interaction of sodium bicarbonate with citric acid so that

the tablets can expand and can float. The oral drug delivery

route is the most preferred because it is easy to use.

Absorption of oral drugs mostly occurs in the stomach and

the intestines.

Conclusion: Therefore, it is necessary to have a drug

delivery system that can extend the contact time with the

stomach, namely the Gastroretentive Drug Delivery System

(GRDDS).

Keywords: drug, GRDDS, floating system

*Correspondent Author: Nurhalifah

Email: fm19.nurhalifah@mhs.ubpkarawang.ac.id

Nurhalifah, Prayoga Daffa Sundawan, Santika Citra Veronita, Shella Imka Puji Destria, Siti

Nuryamah, Nia Yuniarsih / JOSR: Journal of Social Research, 2(1), 126-133

Literature Review Article: Drug Delivery System Held in the Stomach

(Gastroretentive) 128

INTRODUCTION

Medicine is an ingredient that aims to be used in determining diagnosis, preventing,

reducing, and curing diseases or symptoms of diseases, wounds, or abnormalities of the

body and spiritually in humans or animals, improving the body or parts of the human body

(Wardani, 2021).

According to (Martien et al., 2012) medicine is a substance that through its

chemical effects brings changes in biological functions. Drug molecules interact with

special molecules in biological systems that act as regulators in this case receptors. To

chemically interact with its receptors, the drug molecule must have the appropriate size,

shape of the electric charge, and atomic composition. Currently, many considerations

underlie the development of technology for pharmaceutical therapy consisting of three

main factors, namely effectiveness, suppressing the effects of harm on the system if applied

(safety), and acceptability to patients (acceptability).

In the process of discovering new pharmaceuticals, pharmaceutical preparation

formulation technology and drug delivery systems played an important role. The main

factors that are generally considered in this field include molecular and physicochemical

considerations such as molecular equilibrium, hydrophilic-lipophilic equilibrium,

biopharmaceutical processes, metabolism and biodegradation, drug-receptor affinity,

physiological considerations, and biocompatibility (Martien et al., 2012). This delivery

system serves to direct the drug molecules to the desired target. This encourages the

development of drug delivery systems, especially in terms of formulations to optimize the

use of additives to obtain a drug preparation with a good delivery system and meet the

therapeutic effect.

The oral drug delivery route is the most preferred because it is easy to use.

Absorption of oral drugs mostly occurs in the stomach and the intestines. Imperfect

absorption in the stomach is caused by the Gastro Residence Time (GRT) factor. The

presence of gastric emptying time causes the drug to not be in the stomach for a long time

so it is necessary to increase GRT. The longer the drug stays in the stomach, the more

absorption of the drug so that the bioavailability of the drug also increases. Therefore, it is

necessary to have a drug delivery system that can extend the contact time with the stomach,

namely the Gastroretentive Drug Delivery System (GRDDS). There have been many

studies on GRDDS formulations, including Nifedipine and Nilotinib formulations to

increase bioavailability, antibiotics to increase the effectiveness of drugs against H. pylori

treatment, ofloxacin as a delayed release drug delivery system, increasing the solubility of

verapamil drugs, furosemide, propranolol, and others (Annisa, n.d.-a).

The GRDDS delivery system is a sustained drug delivery system that can hold

drugs back in the stomach for a longer time. The advantages of GRDDS include being able

to increase bioavailability, increase the solubility of drugs that are poorly soluble in high

pH, can control of therapeutic levels to reduce the occurrence of fluctuations, can extend

the half-life so that the frequency of drug administration can be reduced. However, this

system is not suitable for use in drugs that irritate the stomach, are unstable in gastric pH,

or experience significant first-pass effects. There are several systems in the GRDDS

formulation, namely floating, aggressive, high density, superiors, expandable, raft forming,

and magnetic (Annisa, n.d.-b). This study aims to describe the types of GRDDS

preparations. The variation is due to a combination of differences in mechanisms and

technology.

Nurhalifah, Prayoga Daffa Sundawan, Santika Citra Veronita, Shella Imka Puji Destria, Siti

Nuryamah, Nia Yuniarsih / JOSR: Journal of Social Research, 2(1), 126-133

Literature Review Article: Drug Delivery System Held in the Stomach

(Gastroretentive) 129

RESEARCH METHODS

This research is by using the Literature Review design where a literature review is

a writing method looking for literature from international or national, this literature can be

obtained based on journals, books, the internet, or from other library sources, the design in

this study uses systematic review reviews of review documents that identify, assess and

interpret all findings on a topic research, to be predetermined later as an effort made by the

researcher in finding information related to the problem under study.

Criterion

Inclusion

Conclusion

Timeframe and population

10-year journal, i.e. year

(2012-2022)

International and national

journals whose year span is

below 2012

Language

Journals took in Indonesian

(National) and English

(International)

International journals with

languages other than

English such as Arabic,

Chinese, etc.

Subject

Journal with drug delivery

system material

Journal with material on the

delivery system of drugs

held in the field

Journal Content Theme

Discharged drug delivery

system (GRDDS)

Route of delivery of the

drug through the stomach

Types of Journals

Fulltext research journal

Journals are not full-text

research

(Table 1. Inclusion and Exclusion Criteria)

RESULTS AND DISCUSSION

Based on searching for data sources, information was obtained about several

descriptions of the drug delivery system that was withheld in the drug. Shown in Table.2

Reference

Article title

Method

Result

Data

based

Mohamma

d Zulfikhar

A.1, Dwi

Nurahmant

o2, Lusia

Oktora

R.K.S,

2019

HYDROXYPRO

PYL

METHYLCELL

ULOSE

OPTIMIZATIO

N AND

CHITOSAN ON

FLOATING-

MUCOADHESI

VE TABLETS

CIMETIDINE

FACTORIAL

DESIGN

METHOD

Research

method with

Powder

making for

floatingmuco

adhesive

tablets

cimetidine.

Creation of floating

tablet systems

Cimetidine is made

using the method

effervescent with the

addition of gas

generating systems

i.e. citric acid and

sodium bicarbonate.

Drug floating system

hull can be made

using making

air-filled chambers or

inert gases that

Google

Scholar

Nurhalifah, Prayoga Daffa Sundawan, Santika Citra Veronita, Shella Imka Puji Destria, Siti

Nuryamah, Nia Yuniarsih / JOSR: Journal of Social Research, 2(1), 126-133

Literature Review Article: Drug Delivery System Held in the Stomach

(Gastroretentive) 130

formed as a result of

gas-generating

interactions

a system with gastric

juices

Eva

Setyorini,

Eka Deddy

Irawan,

Lusia

Oktora

Ruma

Kumala

Sari, 2021

Optimization of

Hydroxypropyl

Methylcellulose

and Xanthan

Gum on

Floating-

Mucoadhesive

Gliclazide

Tablets Factorial

Design Method

(Optimization of

Hydroxypropyl

Methylcellulose

and Xanthan

Gum on

Floating-

Mucoadhesive

Gliclazide

Tablet using

Factorial

Design)

The study is

conducted by

the method of

factorial

design. The

optimized

factor is

amount of

polymer

HPMC K4M

and xanthan

gum

Complete

formula

arrangement

Floatability

parameters

what was tested in

this study was

floating lag

time and floating

duration time.

Requirement

The floating lag time

chosen is between 10-

600

seconds with the goal

that the tablet can

floats right in the hull

and gives

good buoyancy.

Floating

requirements

The duration time

chosen is no less

of 12 hours. The

response is generated

later

processed using

software design

expert

version 9.0.6.

Google

Scholar

Vivianne

Annisa,

2021

Review:

Gastroretentive

Drug Delivery

System

(GRDDS)

Literature

Method

Review

there are many types

of GRDDS

preparations. The

variation is due to a

combination of

differences in

mechanisms and

technology. Each

type of system has its

advantages and

disadvantages.

Several types of

GRDDS preparations

have been produced

by the

pharmaceutical

industry and

marketed. The most

widely applied

systems by the

Google

Scholar

Nurhalifah, Prayoga Daffa Sundawan, Santika Citra Veronita, Shella Imka Puji Destria, Siti

Nuryamah, Nia Yuniarsih / JOSR: Journal of Social Research, 2(1), 126-133

Literature Review Article: Drug Delivery System Held in the Stomach

(Gastroretentive) 131

pharmaceutical

industry are floating

and bioactive

systems. Examples of

trademarks that have

been marketed are

Zanocin, Riomet,

Cifran, Madopar,

Prolopa, Valrelease,

Xifaxan, Cytotec,

Conviron, and many

(Table 2. Data source Overview of Nutritional Status in tuberculosis Patients)

1. Effervescent with the addition of gas-generating systems, namely citric acid and sodium

bicarbonate. The floating system of the drug can be made by creating a space filled with

air or inert gases formed due to the interaction of generating system gases with gastric

juices). Floating systems can use expandable polymeric materials such as HPMC and

chitosan. The floating mechanism begins with the contact of gastric juices with tablets

which causes the polymer to hydrate to form a gel layer that can withstand CO2 gas

formed due to the interaction of sodium bicarbonate with citric acid so that the tablets

can expand and can float. Table 5 shows the floating lag time capability of formula

AB> A> (1)>B, while for floating duration time all formulas give the same result that

they can float for more than 12 hours. Based on the results of testing the ability to float

lag time tablets in table 5, it shows that the use of HPMC with a high-level concentration

in formula A compared to formula (1) and formula AB compared to formula B can

prolong the floating lag time, while the use of chitosan at high levels in formula AB

compared to formula A can prolong the floating lag time Tablets. The use of low levels

of HPMC and chitosan can speed up the floating lag time of tablets, but in formula (1)

low levels of chitosan produce a longer floating lag time than the use of high levels of

chitosan in formula B. Coded factor equations from software design expert version 11

of HPMC polymers and Chitosan shows positive values in the floating lag time

response, this shows the use of both polymers can increase the floating lag time. HPMC

and chitosan are hydrophilic hydrocolloid polymers that can form barrier gels with high

viscosity, to slow down the penetration rate of gastric juices and result in fewer and

fewer gas-generating agents in contact with gastric juices to increase floating lag time

tablets.

2. Obtaining uniformity of gliclazide powder in the mixture of powder and tablet content

shows that all formulas meet the range of % content of active ingredient gliclazide (85.0-

115.0%) and CV <6% so that it can be said to be a uniform sample [10]. Testing the

mechanical strength of tablets aims to avoid the influence of other variables that may

result from the physical properties of tablets. The results of the tablet's mechanical

strength test showed that all yield formulas met the criteria of 10-20 kg hardness [11]

and the brittleness (<1%) [12]. The floatability parameters tested in this study are

floating l time and floating duration time. The selected floating lag ti requirement is

between 10-600 seconds with the aim that the tablet can float right in the hull and

provide good buoyancy. The selected floating duration time requirement is not less than

12 hours. The resulting response is then processed using software design expert version

9.0.6 from Equation 1, it is known that the use of HPMC K4M polymers and xanthan

gum gives positive values indicating a slowdown in floating lag time. The effect of the

HPMC K4M factor and the effect of the xanthan factor gives negative values indicating

an acceleration of floating lag time. The results of the great mucoadhesive strength test

Nurhalifah, Prayoga Daffa Sundawan, Santika Citra Veronita, Shella Imka Puji Destria, Siti

Nuryamah, Nia Yuniarsih / JOSR: Journal of Social Research, 2(1), 126-133

Literature Review Article: Drug Delivery System Held in the Stomach

(Gastroretentive) 132

on the AB formula with the results of the AB>A>B> (1) formula. The test results can

be seen in Table 3. The mucoadhesive strength response was further analyzed with

software design expert version 9.0.6. Equation 2, shows that the effect of the HPMC

K4M factor and the effect of the xanthan g factor gives a positive value that there is an

increase in mucoadhesive strength and the interaction effect gives a negative value that

there is a decrease in mucoadhesive strength. Determination of the parameters of DE720

is aimed at obtaining an idea of the percentage of drugs released in plasma. The DE720

response value is then analyzed with software design expert version 9.0.6 Equation 3, it

shows that the factor effect of HPMC K4M, xanthan g, um, and the interaction of the

two gives a positive value. The effect of HPMC K4M and xanthan g interaction factors

gave the greatest DE720 response value compared to the single-factor effect. The

magnitude of the response value resulting from the effect of the interaction factor

HPMC K4M and xanthan gum shows a dominant influence on the DE720 value of

tablets, namely increasing the DE720 response that there is an increase in DE720 Table

4. indicates that r2 in formulas A, B and AB is high so that formulas A, B, and AB

denote zero-order discharge models. While the value of r2 in formula (1) follows the

Higuchi model.

3. The development of a sustained-release drug delivery system, namely GRDDS has the

potential to increase bioavailability because it can extend GRT. In addition, GRDDS

can also control drug delivery so that the plasma concentration of drugs can be

controlled within a certain period. The GRDDS approach can go through various means,

such as floating, aggressive, high-density, super porous, expandable, raft forming, and

magnetic systems. Floating systems can go through two manufacturing mechanisms,

namely effervescent and non-effervescent. The development of GRDDS has been

carried out by the pharmaceutical industry and has been widely marketed. The

application of GRDDS has the potential to be developed in other drugs that have low

absorption problems in the upper gastrointestinal tract or have a short half-life

CONCLUSION

The oral drug delivery route is the most preferred because it is easy to use.

Absorption of oral drugs mostly occurs in the stomach and the intestines. Therefore, it is

necessary to have a drug delivery system that can extend the contact time with the stomach,

namely the Gastroretentive Drug Delivery System (GRDDS). The GRDDS delivery system

is a sustained drug delivery system that can hold drugs back in the stomach for a longer

time. The advantages of GRDDS include being able to increase bioavailability, increase

the solubility of drugs that are poorly soluble in high pH, can control of therapeutic levels

to reduce the occurrence of fluctuations, can extend the half-life so that the frequency of

drug administration can be reduced.

BIBLIOGRAPHY

Annisa, V. (n.d.-a). Sistem Penghantaran Obat Gastroretentif (GRDDS).

Annisa, V. (n.d.-b). Sistem Penghantaran Obat Gastroretentif (GRDDS).

Martien, R., Adhyatmika, A., Irianto, I. D. K., Farida, V., & Sari, D. P. (2012).

Perkembangan teknologi nanopartikel sebagai sistem penghantaran obat.

Majalah Farmaseutik, 8(1), 133–144.

Nurhalifah, Prayoga Daffa Sundawan, Santika Citra Veronita, Shella Imka Puji Destria, Siti

Nuryamah, Nia Yuniarsih / JOSR: Journal of Social Research, 2(1), 126-133

Literature Review Article: Drug Delivery System Held in the Stomach

(Gastroretentive) 133

Wardani, B. K. (2021). Pengaruh Pelayanan Kefarmasian Terhadap Kepuasan

Pasien Di Apotek Berkah Santosa Klaten. IJMS-Indonesian Journal on

Medical Science, 8(2).

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license (https://creativecommons.org/licenses/by-sa/4.0/).