Sarsam college of pharmacy, Palshiwadi, baramati.
The formulating floating beads of Saxagliptin increase the gastric residence time so that beads retain in stomach for extended period of time, increases duration of drug release and improvesbioavailability. Floating drug delivery system helps to reduce the dosing frequency and total dose of drug, improves patient’s compliance and convenience, maintains plasma drug level andreduces gastrointestinal side effects.
Oral dosage forms known as gastroretentive dosage forms have the capacity to be retained in the GI system and to withstand rapid stomach emptying. These systems are ideal for medications with narrow absorption window. They are created as formulations of modified release drug delivery systems that can be site-constrained in the GIT (stomach) and have the capacity to adjust the release rate. The efficiency of gastroretentive drug delivery systems is influenced by a number of variables, including dietary effects, stomach transit duration, and the medication's location of absorption. asy storage and transport of the drug, controlled delivery, flexibility in formulation and generally reduced pricing when compared to other dosage forms. The common objective of drug delivery systems is to achieve a systematic drug that could be taken as a single dosage form. Especially when the drug in question is to be taken periodically throughout the patient's life. An incorporated single unit dosage form would also reduce the frequency of medical administration. It should also be noted that even though it is the easiest form of drug delivery, in case of emergencies oral dosage forms are not applicable due to their slow absorption rate.
Anatomical and physiological barrier for gastrointestinal drug delivery system:
Stomach:
The majority of gastric retention occurs here. The formulation of GRDDS must take into account its anatomy and physiology. The stomach is situated in the upper region of the abdomen, just below the diaphragm. Its volume varies depending on how much it is distended after meals and can reach up to 1500 ml; however, once food has been emptied, it collapses to a resting volume of 25 to 50 ml. [1]
Anatomically, there are three parts of the stomach:
1. Fundus
2. Body
3. Antrum (pylorus).
Following a meal, a stomach typically has a volume of 1.5 liters, varying between 250 and 500 ml during the inter-digestive stages. The body and fundus, which make up the proximal portion, serve as a storage area for undigested materials, whereas the antrum serves as the primary location for mixing motions and serves as a pump for gastric emptying by accelerating the actions. [1]
Gastric emptying and gastric motility:
In both the fed and fasted states, the stomach empties. However, there are two states where the motility patent is unique. A series of electrical events known as the inter-digestive cycle pass through the stomach and intestines every two to three hours while someone is fasting. The migrating myoelectric cycle (MMC), also known as the inter-digestive myoelectric cycle, is the mechanism that causes this. [1]
The four phases of the migrating myoelectric cycle (MMC), as described by Whilson and Washington, are as follows.
Gastric Motility: A complex network of neuronal and hormonal cues controls the movement of the stomach. The vagus nerve, the sympathetic nervous system, the enteric nervous system, and the parasympathetic nervous system all participate in neural regulation. Numerous hormones have an impact on gastric motility; for instance,cholecystokinin and gastrin both calm the proximal stomach while increasing the distal stomach contractions. The final result of smooth muscle cells integrating a wide range of inhibitory and stimulatory impulses is most likely the pattern of stomach motility. [1]Gastric emptying rates were determined using scintinographic studies, which showed that controlled-release dosage forms taken orally are primarily affected by two issues:
1. The Short GRT (Gastric Residence Time)
2. Variable Gastric Emptying Time (Gastric Emptying Time)
Methods for dealing with gastric retention or the mechanistic elements of GRDFS:
To extend the gastric residence time, a variety of methods are currently being used, including bioadhesive systems, floating systems, high-density systems, swelling or expandable system.
Method of Preparation of floating beads:
Ionotropic Gelation Method:
The floating beads of Saxagliptin were prepared using the sodium alginate as gelling agent, calcium chloride as crosslinking agent, calcium carbonate as gas forming.
Saxagliptin alginate beads were made using the ionotropic gelation technique. Sodium alginate was dissolved in 20 ml of distilled water and stirred continuously. Saxagliptin and calciumcarbonate were added to the above solution. The mixture was set aside for 25 minutes to allow air bubbles to escape. This mixture was extruded into a solution of calcium chloride using a syringe. The beads were gathered, washed with distilled water, and then set to dry. Sodium alginate (gelling agent) was selected as an factor.
Table no 01: Formulation Table
In vitro evaluation of formulated floating beads of Saxagliptin.
Uniformity of content:
The drug content of the beads was determined by taking 50 mg beads of each formulation. 50 mg from each formulation were accurately weighed and triturated in a mortar and pestle. In the 100
ml of 0.1N HCL, the beads powder was added. It was stirred for 2hours using a magnetic stirrer. From this solution, 1 ml was withdrawn and added to a 10 ml volumetric flask, and finally the volume was made to 10 ml with 0.1 N HCL (10?g/ml), then the solution was filtered with Whatman filter paper, and the absorbance of the resulting solution was measured at 272nm using a UV spectrophotometer.
Drug content = Actual drug content / Total Weight of beads ×100
formula. Drug entrapment = (Practical drug content / Theoretical drug content) x100
In Vitro buoyancy study:
50 individual floating beads were introduced to 100 ml of simulated stomach fluid (pH 1.2), which was kept at 37.50C and swirled at 100 rpm with a magnetic stirrer. The quantity of floating beads was visually counted every hour for the next 12 hours. The number of beads floated were calculated by the following equation: % Floating beads = Floating beads / Total beads × 10
Characterization of formulated floating beads of saxagliptin.
Partical size:
Table No.2 Partical Size Analysis
All formulations were round in particle shape with smooth surface. The mean particle size of beads of saxagliptin ranged from 81.23to 95.24µm. The mean diameter of prepared beads was increased with an increase in sodium alginate concentration (F1-F6) due to increased viscosity of solution which influence the interaction between disperse metphase and dispersion medium that affect the size distribution of particle.Decreasing the sodium alginate concentration to 1% W/V resulted in clumping of the beads after drying whereas high concentration alginate (2% to 3%W/V) resulted free flowing beads.This could be attributed to an increase in relative viscosity at higher concentration of polymer and formation of larger particle. [38,69]
Percentage Yield
The studies were conducted, and the maximum percentage yield was found to be 92.24%
with F6 batch and minimum of 80.76% with batch F1. [68]
Table No.3 Formulations Percentage Yield
The studies were conducted, and the minimum percentage yield was found to be 80.23% with F1 batch and maximum of 92.24% with batch F6. [68]
Drug Content The data for drug content of floating beads of Saxagliptin is as shown below
Drug Content
Table No.4 Drug Content
All values are expressed as mean . Determination of drug content was carried out to quantify the amount saxagliptin in prepared beads, it was found to be in range 68.87% to 93.45%. The all six batches’ results are shown in Table indicating drug content improved with an increase in sodium alginate concentrations. Enhanced drug content with an increase in sodium alginate concentration could be due to enhanced availability of the calcium binding site in anionic liner polysaccharide chain and consequently. [69]
Entrapment Efficiency
Table No. 5 Entrapment Efficiency
The determined encapsulation efficiency of prepared Saxagliptin beads is elaborated in Table. On examination of the results, an increase in percent entrapment efficiency from78.23 to 96.87 entrapment efficiency also increased. Additionally, the increased viscosity, which is directly related to polymer concentration, hindered drug mobility, which had an impact on entrapment efficiency. [67, 68]
In Vitro Buoyancy Study
Table No.6 Invitro Buoyancy Study
The shows the in vitro buoyancy data of Saxagliptin beads in simulated gastric fluid pH 1.2. all formulation had a lower density than simulated gastric fluid. The in vitro floating study revealed that all formulation had excellent floating ability. due to the formation of air bubbles during preparation, the beads containing gas producing agent floated for longer than 12 hours. [12]
In vitro Dissolution Study:
In vitro dissolution profile of formulation F1, F2,F3
Table No.7 Dissolution of F1, F2, F3
TableNo.8 In vitro dissolution profile of formulation F4, F5, F6
The floating beads were subjected to in-vitro release using paddle type 2 dissolution apparatus in 900ml of 0.1 N HCl medium. The dissolution profile of pure Saxagliptin alginate beads given in table The release of all formulation observed was between 74.87% to 90.36% The polymer concentration (1%W/V sodium alginate) shows release , 74.64 to 90.36 respectively
CONCLUSIONS
The objectives of the study were to develop sodium alginate beads for intragastric delivery of Saxagliptin.The beads were prepared by the gelation technique using calcium chloride as a crosslinker and calcium carbonate as a gas-forming floating inducer. The entrapment efficiency of alginate beads was significantly improved after the inclusion of sodium alginate in the matrices,and we compared formulated beads by using sodium alginate with beads formulated by pectin as natural polymer. Various aspects of the formulation, its characterization are particle size, percentyeild, drug content, drug entrapment efficiencyand dissolutionstudies. . The best formulation from batches F1-F6, found to be excellent practical size 81.23-95.24 Percentage yield,from 80.23-92.24% entrapment efficiency 78.23-96.87 and Invitro Dissolutin 76.64-90.36 and release of drug, was batch F2 with drug release of 74.36% hence It shows the microspheres formulated by using sodium alginate shows excellent results.
REFERENCE
Rutuja Nikam, Tejas Kamthe, Sayali Londhe, Nikhil khomane, Formulation And Evaluatin Of The Stomach Specific Drug Delivery System Of Saxagliptin, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 7, 1476-1483. https://doi.org/10.5281/zenodo.12787955
10.5281/zenodo.12787955
