A Review on Gastro Retentive Drug Delivery Systems with the Special Focus on Floating Drug Delivery

Abstract

Gastro Retentive Drug Delivery System is one of the novel approach and all researchers in pharma industries are focused in the same. The main aim of writing this review on Gastro Retentive floating drug delivery systems is to assemble the recent literature with special emphasis on its principal mechanism of floatation to achieve gastric retention and its recent development. Floating systems are low density systems that has density lower than gastric fluid and floats over the gastric fluid and remains buoyant in the stomach without affecting the gastric emptying rate for a prolonged period of time. Floating dosage forms can be formulated as tablets, capsule. This review article includes detailed information about its classification, advantages and in-vitro evaluation parameters. *Corresponding Author Email: [email protected] Received 10 January 2019, Accepted 21 January 2019 Journal home page: http://www.ajptr.com/ Kharvi et. al., Am. J. PharmTech Res. 2019; 9(01) ISSN: 2249-3387 39 www.ajptr.com INTRODUCTION Oral administration is one of the most appropriate and widely used route for drug to show the systemic effect. The drugs that are well absorbed in the GIT, gets degraded in the intestine, and have a short half-life requires the frequent dosing to achieve the specific therapeutic activity. The development of oral sustained or controlled release formulation, such as gastro retentive drug delivery system can be an attempt to release the drug slowly into GIT for prolonged period and maintain an effective drug concentration in the systemic circulation. The complete absorption of the drug in the absorption site can be prevented by the rapid gastrointestinal transit and can reduce the therapeutic efficacy of the dose that is administered. Most of the drugs are absorbed in the stomach or upper part of small intestine. Gastro-retentive Drug Delivery System (GRDDS) are the type of dosage forms that retains in the stomach. The gastric retention of solid dosage forms can be achieved by different mechanisms such as floating system, sedimentation, modified shape systems, expandable systems etc. FDDS is one of the most feasible approach for achieving the gastric retention for prolonged period. The bulk density of the floating drug delivery system is lower than the gastric fluid thus they remain buoyant in the stomach for longer period of time without affecting the gastric emptying rate. The Gastro-retentive dosage forms on contact with the gastric fluid forms the colloidal gel barrier around the surface, the gel barrier is impermeable to water and thus maintains the bulk density less than one and remains buoyant in the stomach until the entire dose is released. These type of dosage forms remains in the gastric region for several hours and hence considerably increases the gastric residence time of the drugs. The FDDS are mainly useful for drugs that are absorbed in the upper part of the gastrointestinal tract, and drugs that are less soluble in GIT or are degraded by the alkaline pH may benefit from prolonged gastric retention. The FDDS are also useful for local and sustained drug delivery to the stomach and proximal small intestine to treat certain condition, prolonged gastric retention of the drug may offer several advantages together with improved bioavailability and therapeutic efficacy, reduction in dose frequency and possible reduction of the dose size. PHYSIOLOGY OF GIT: GIT system has a complex anatomy and physiology. Variation in pH, bile contents, enzyme activity etc. can influence the dissolution, release and absorption of drug in GIT from the dosage form. The Gastro-intestinal tract is essentially a tube about nine meters long that runs through the middle of the body from the mouth to the anus and includes the throat (pharynx), esophagus, stomach, small intestine (consisting of the duodenum, jejunum and ileum) and large intestine (consisting of the Kharvi et. al., Am. J. PharmTech Res. 2019;9(01) ISSN: 2249-3387 www.ajptr.com 40 cecum, appendix, colon and rectum). Mainly the stomach is divided into three regions the Fundus, Body and Antrum (pylorus). \uf076 Body: It acts as a reservoir for undigested materials. \uf076 Fundus: Proximal part of stomach. \uf076 Antrum: It is the main site for mixing motion and act as a pump for gastric emptying propelling action. Migrating Myoelectric Cycle (MMC): Gastric emptying takes place both in fed and fasting states, the pattern of motility differs in both the states. Due to this bioavailability of drug administered orally is different, because it depends upon the state of feeding. During fasting state inter-digestive series of electrical event takes place between stomach and intestine which is called as inter-digestive myoelectric cycle or migrating myoelectric cycle (MMC). It is divided into four phases-: 1. Phase-I-: It is a basic phase, remains for 30-60 minutes, it does not have any secretory activity and contractile motion. 2. Phase-II-: It is also known as pre-burst phase, intermittent contractions occur and it last for 20-40 minute. As the phase progresses the intensity and frequency also increases gradually. 3. Phase-III-: It is known as burst phase; remains for 4-6 minutes. It includes intense and regular contractions for short time. It is due to wave that all the undigested material is moved out of the stomach down to the small intestine. It is also known as the housekeeper wave. 4. Phase-IV-: It remains for 0-5 minute, occur between Phase III and Phase I. After ingestion of the meals, the pattern of contraction changes from fasted to feed state. These contractions result in reducing the size of food particles to less than 1 mm which is then pushed in the form of suspension towards the pylorus. Kharvi et. al., Am. J. PharmTech Res. 2019; 9(01) ISSN: 2249-3387 41 www.ajptr.com Different features of stomach: Gastric pH: Fasted healthy subject 1.1 ± 0.15 Fed healthy subject 3.6 ± 0.4 Volume: Resting volume is about 25-50 ml Gastric secretion: Acid, pepsin, gastrin, mucus and some enzymes about 60 ml with approximately 4 mmol of hydrogen ions per hour. Effect of food on Gastric secretion: About 3 litres of secretions are added to the food. Gastro Intestinal transit time increase. FACTORS AFFECTING GASTRIC RETENTION: The factors that affects the gastric emptying of an oral dosage form are as follows, \uf0d8 Density: Gastric resident time (GRT) of dosage form buoyancy that is dependent on the density. If the dosage form is having density less than the gastric fluid which can increase the GRT. \uf0d8 Size: Dosage form having a diameter of 7.5 mm has reported to have an increased GRT when compared with the dosage form having diameter of 9.9 mm. \uf0d8 Shape: Tetrahedron and ring shaped devices remains in the stomach for longer period of time with better GRT up to 90-100% retention at 24hrs when compared with the other shapes like planar disc, planar multi lobe, continuous stick and string. \uf0d8 Single or multiple unit formulation: Multiple unit formulations show a more obvious release profile and minor impairing of performance due to failure of units, allow co-administration of dosage form units with different release profiles or containing incompatible substances and permit a more safety against dosage form failure compared with single unit dosage forms. Multiple unit formulations are more reliable as compared to single unit formulations, which suffer “all or none concept”. The units of multiple unit systems are freely distributed throughout the GI tract. \uf0d8 Fed or unfed state: Under fasting conditions, the GI motility is affected by the period of the migrating myoelectric complex (MMC) that occurs every 1.5 to 2 hours. The MMC pushes the Kharvi et. al., Am. J. PharmTech Res. 2019;9(01) ISSN: 2249-3387 www.ajptr.com 42 undigested material from the stomach, and if the time of administration of the formulation coincides with the MMC, the GRT of the dosage for unit can be expected to be very short. However, in the fed state, MMC is delayed and GRT is considerably longer. \uf0d8 Nature of meal: Feeding of indigestible polymers or fatty acid salts such as cellulose, starch, reffinose and poly-dextrose can delay MMC by changing motility pattern of the stomach, thus can decrease the gastric emptying rate, increases the GRT of the dosage form. \uf0d8 Caloric content: GRT can be increased by 4 to 10 hours with the meal containing high proteins and fats can increase the GRT to up to 4-10 hours. \uf0d8 Frequency of feed: The GRT can increase by 400 minutes when successive meals are given compared with a single meal due to the low frequency of MMC. \uf0d8 The resting volume of the stomach is 25 to 50 ml. Volume of liquids administered affects the gastric emptying time. When volume is large, the emptying is faster. Biological factors such as: \uf0d8 Gender: GRT in males around (3.4±0.6 hours) compared with their age and GRT of female around (4.6±1.2 hours), regardless of the weight, height and body surface. \uf0d8 Age: Geriatrics, especially those over 70, have a significantly longer GRT, normal adult’s men have faster gastric emptying rate when compared to women and old people. \uf0d8 Stress can increase the gastric emptying rate while it is decreased in case of depression. \uf0d8 Posture: GRT can vary between supine and upright ambulatory states of the patient. SUITABLE DRUG CANDIDATES FOR GASTRO-RETENTIVE DRUG DELIVERY SYSTEM: 1. Generally, the ideal candidates for GRDDS are molecules that have poor intestinal absorption but having the better absorption in the upper part of the GIT. 2. Acts locally in the stomach. 3. Primarily absorbed in the stomach. 4. Poorly soluble at an alkaline pH. 5. Absorbed rapidly from the stomach. 6. Degrade in the colon. 7. It should be absorbed primarily in the duodenum and upper jejunum segments. e.g. Calcium is mainly absorbed in the duodenum. 8. Drugs which have a short half-life and require frequent dosing. 9. Drugs which undergoes first pass metabolism. Kharvi et. al., Am. J. PharmTech Res. 2019; 9(01) ISS