INTRODUCTION:

The main aim of any drug delivery system is to provide a therapeutic amount of drug to the particular site of action in the body to maintain the desired amount of drug concentration. Oral administration is the most convenient route of any drug delivery to systemic circulation due to the ease of administration, patient compliance, flexibility in formulation.Some of the orally administered drugs show poor bioavailability when administered as a conventional dosage form1,2.

The amount of drug which is required to be absorbed is less than the desired value. Drugs which are readily absorbed from gastrointestinal tract and have a shorthalf-life and are eliminated quickly from systemic circulation. Therefore frequent dosing of this drug is required to achieve the desired therapeutic activity.To avoid this limitation Gastro retentive drug delivery system (GRDDS) has been introduced. It is an approach whichreleases the drug slowly into the gastrointestinal tract and maintains effective drug concentration in the body for a prolongedperiod3,4.

Gastroretentive drug delivery system specifically releases the drug to its active site by prolonging the gastric residence time. These can be categorized into a high-density system where the prepared formulation is retained in the extremity of the stomach,and hence a sustained action is seen or a low-density system where the use of buoyancy technique helps to make the formulation to float in the gastric fluid5-7. Moreover, the mucoadhesive system can also be formulated where bioadhesion of the prepared tablets with the stomach mucosa takes place. These delivery systems have immense potential to increase local absorption from the stomach and duodenum. The conventional delivery system led to the deficient release of drug from the delivery system and a high drug degradation which was overcome by gastro retentive drug delivery. The class II drugs of BCS system which are having low solubility can also be formulated into GRDDS as the high pH environment of the stomach increases its solubility8.

In the present study, graduates have gathered the information from the available resources and compiled the article so that it can be available to them in published form. Although the subject is explored one, the intention for the publication of the present work is to seed the interest towards the publication so that they can learn the process thoroughly.

CLASSIFICATION

Gastro retentive dosage form can be broadly classified into the effervescent system and non-effervescent system9-11.

1) Effervescent system

The effervescentsystem comprises of CO₂ which causes effervescence and hence buoyancy is maintained in the stomach for an extended period.

a. Gas generating system:Effervescent components like sodium carbonate liberate carbon dioxide after reaction with acidic environment of the stomach which entangle with the formed hydrocolloids and thus results in the upward movement of the drug maintaining its buoyancy.

b. The volatile liquid containing system. : these make intra gastric floating GIDDS,inflatable, intragastric osmotically CDDS.

2) Non-effervescent system

These work by floating the prepared formulation using the phenomenon of buoyancy in the gastric fluid. These can be further divided into other systems like Colloidal gel barrier system, Microporous compartment system, Floating microspheres,Alginate floating beadsand Raft-forming system.

PHYSIOLOGY OF STOMACH

The gastrointestinal tract is essentially a long tube of about 9m which extends from mouth to anus. Its main function is to take nutrients and excrete out waste products by the process such as digestion, absorption, secretion, and excretion. The stomach is mainly divided into fundus, body,and pylorus. The stomach mainly performs the function of storing the food temporarily, grinding it and releasing it slowly into the duodenum12, 13.

Anatomically the stomach is divided into three regions: fundus, body, and antrum (pylorus)14(fig. 1). Undigested materials are stored in the proximal part of fundus and body whereas the antrum acts as a pump for gastric emptying using propelling actions. Moreover, it is also the main site for mixing motions of the ingested food15,16.

Figure 1: Anatomy of the stomach

Gastric motility and empty gastric rate

There are two different patterns of gastrointestinal motility and secretion which exist in the fasted and fed state. Bioavailability of orally administered drug mainly depends upon the state of feeding. During the state of fasting, it is characterized by an inter-digestive myoelectric cycle or migrating cycle17.

It can be divided into four phases:

· Phase I (Basal phase):It lasts for40-60 min with rare contractions

· Phase II(Preburst phase):It lasts for 40-60 min with intermittent potential and contractions.

· PhaseIII (burst phase):It lasts for the very short period of 4-6 min with intense and regular contraction. During these contractions, the undigested food is swept from the stomach into the intestine. They are also called as housekeeper waves.

· Phase IV:It lasts for 0-5 min and takes place between phase III and I for two consecutive cycles18-20 (fig. 2).

Figure 2: An inter-digestive myoelectric cycle during a state of fasting

APPROACHES TO GASTRORETENTION

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

1) High-density System

The high-density systems have more density as compared to the contents present in the stomach(1.004 gm/cm³) which retain the drug system in the lower part of the stomach. For the high-densitysystem,sedimentation can be employed as a retention mechanism.GRT ~3 g/cm³densityis required for the sufficient prolongation. The pellets are the high-density formulation which can be used,and it can be coated with heavy, nontoxic materials such as titanium dioxideetc.21, 22

2) Swelling and expanding system

These systems are also termed as "plug type system" since they tend to remain lodged at the pyloric sphincter. This type of drug delivery system is retained into the stomach by increasing its size. The extensive swelling of these polymers is due to the presence of physical/chemical/crosslinks thus preventing the dissolution of the polymer and hence maintains the physical integrity of the dosage form23-25.

3) Bioadhesive or Mucoadhesive systems

Bio/mucoadhesive systems are those which bind to the gastric epithelial cell surface or mucin which extends the gastro-retentive time in the stomach. Therefore, the bioavailability is increased. The various mucoadhesive polymer such as cationic (polybrene,polylysine),anionic(dextran sodium) and neutral polymers like bovine serum albumin (BSA) are frequently used for mucoadhesive drug delivery. The proposed mechanism of mucoadhesion is the formation of electrostatic and hydrogen bonding at the mucus polymer boundary26,27.

4) Floating systems

Floating drug delivery systems (FDDS) have a bulk density less than gastric fluids and so remain buoyant in the stomach without affecting the gastric emptying rate for a prolonged period. While the system is floating on the gastric contents, the drug is released slowly at the desired rate from the system. Floatation of a drug delivery system in the stomach can be achieved by incorporating floating chamber filled with vacuum, air, or inert gas28-30.

FACTORS AFFECTING GASTRIC RESIDENCE TIME OF FDDS

1) Formulation Factors

a. Size and shape of tablets:The retention of floating delivery system in stomach depends on the size of tablets. During the digestive phase, small tablets are emptied from the stomach, and large sized tablets are expelledfrom the housekeeping waves. There are six shapes such as (ring tetrahedron, string, pellet,and cloverleaf) which were screened in vivo for their potential ability in gastric retention31-33.

b. The density and viscosity of tablets:Density is the major factor which affects the gastric residence time of drug dosage form. The dosage forms are having density lower than that of gastric fluid experience floating behaviour and greater residence time.Also,Polymers having a low viscosity such as (HPMC K100 LV) helps in improving the floating properties as compared to high viscosity polymers (e.g.,HPMC K4M).Increase in polymer viscosity results inthedecreased release rate of the drug34,35.

2) Idiosyncratic factors

The gastric emptying time of women is found to be slower as compared to men.GRT in meals (3.4+0.4) is less as compared with their age and race-matched female counterparts (4.6+1.2 hours),regardless of the weight, height and body surface. Moreover, the gastric emptying time is found to be lower in elderly subjects as compared to the younger subjects. The variations (intrasubject and intersubject )are observed in gastric and intestinal transit time36.

EVALUATION PARAMETERS

Gastro retentive floating tablets can be evaluated using certain parameters such as buoyancy test, swelling study, in-vitro dissolution studies and drug release.

1. Buoyancy test: It is determined by using USP dissolution apparatus containing 900 ml of 0.1mole/lit HCl as the dissolution medium at 37°C. The time taken by the dosage form to float is termed as floating lag time and the time for which the dosage form floats is termed as the floating or flotation time37.

2. Swelling Study: The floating tablets were weighed individually (Designated as W0) and placed separately in glass beaker containing 200 ml of 0.1 N HCl and incubated at 37°C ± 1°C at a regular 1hrsintervals till 24 hrs.The floating tablets are removed from the beaker,and the excess surface liquid is removed carefully using the tissue paper. The swollen floating tablets were then re-weighed (Wt.),and% swelling index (SI) was calculated using the following formula38.

Swelling index % (SI) = [(Wt.-W0)/ W0] * 100

Where,

S.I. = Swelling index

Wt. = Weight of tablet at time t

Wo = Weight of tablet before placing in the beaker.

3. In vitro Dissolution Studies: The In vitro dissolution study can be done by using United States Pharmacopeia (USP) type II (Paddle) apparatus at a rotational speed of 100 rpm. Exactly 900 ml of 0.1 N HCl is used as the dissolution medium,and the temperature is maintained at 37°C ± 0.5°C. A sample (10 ml) of the solution is withdrawn from the dissolution apparatus at the specified time interval for 24 hrs,and the same volume is replaced with pre-warmed fresh dissolution media. The samples are then filtered through a Whatman filter paper and diluted to a suitable concentration of 0.1 N HCl39,40.

CONCLUSION:

GRDDs offer various potential advantages for drugs with poor bioavailability. Drug absorption in the gastrointestinal tract is a highly variable process and prolonging gastric retention of the dosage form extends the time for drug absorption. The control of gastrointestinal transit of orally administered dosage forms using GRDD systems can improve the bioavailability of drugs that exhibit site-specificabsorption. In future, it can be easily assumed that GRDD systems will become more popular regarding delivering the drug to the systemic circulation with improving efficiency. In all, it was good to see that the students were propelled towards the said target and they have now known the basics of the publication process. Henceforth, this article will prove to be a milestone in their future research carrier.

AKNOWLEDGMENT:

The author wants to show a sincere gratitude to the Rungta College of Pharmaceutical Sciences and Research for providing necessary facilities for the completion of work.

CONFLICT OF INTEREST:

None.

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