INTRODUCTION:

Oral controlled release drug delivery has recently been of increasing interest in pharmaceutical field to achieve improved therapeutic advantages, such as ease of dosing administration, patient compliance and flexibility in formulation. Floating drug delivery systems 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 of time. While the system is floating on the gastric contents the drug is released slowly at the desired rate from the system. This results in an increased GRT and a better control of fluctuations in plasma drug concentration.^1,3Floating drug delivery system (FDDS) is helpful for drugs which have an absorption window in the stomach or in the upper small intestine. It is also helpful for drugs that act locally in the proximal part of gastrointestinal (GI) tract in case of antibiotic administration for Helicobacter pylori eradication in the treatment of peptic ulcer and for drugs that are poorly soluble or unstable in the intestinal fluid.^4,14Floating approach is available in single as well as multiparticulate forms such as beads, microspheres, and pellets.¹⁵Thus, there is a need to develop oral sustained drug delivery system to reside in GIT and release the drug slowly for a long period of time. The bioavailability of drug from its dosage form is influenced by various factors. One of which is gastric residence time. The gastric emptying process from the stomach to small intestine generally lasts from a few minutes to 1-2 hr.⁵

Approaches for Gastro Retention:

Effervescent systems:

· Volatile liquid containing systems

· Gas-generating Systems

Non-effervescent systems

· Colloidal gel barrier systems

· Micro-porous Compartment System

· Hollow microspheres

· Mucoadhesive systems³

Advantages:

1. Improves patient compliance.

2. Bioavailability enhances despite first pass effect because fluctuations in plasma drug concentration are avoided, a desirable plasma drug concentration is maintained by continuous drug release.

3. Freedom from incompatibilities between drug and excipients especially with buffers.

4. Better therapeutic effect of short half-life drugs can be achieved.

5. Gastric retention time is increased because of buoyancy.⁵

Disadvantages:

1. These systems require a high level of fluid in the stomach for drug delivery to float however this can be overcome by using low density polymers.

2. The release rate of the controlled release dosage form varies from a variety of factors like rate of food transit through the drug.

3. Potential toxicity due to loss of integrity of drugs.

4. The dosage forms should be administered with more amount of water (200-250ml).

5. Some drugs present in the floating system causes irritation to gastric mucosa.³

In oral controlled drug delivery systems, the drug is released in predetermined rate with predictable and reproducibility in drug release kinetics. In these dosage forms the rate of drug absorption is equal to rate of drug elimination⁴. Gastroprotective drug delivery system increases gastric retention time hence showing site-directed drug release in upper GIT tract for local and systemic action. The rationale of gaster retentive dosage forms is to prolong gastric residence time to improve the bioavailability of the drugs which are soluble at low pH range.⁷The stomach has three major anatomical regions that are fundus, body and antrum. The action of the gastric juices over the undigested food takes place in the body area while antrum is the area where mixing motions and pumping action occurs, which accounts for the gastric emptying time. The contraction of the stomach occurs at fasting as well as fed state with different electrical events and patterns. The contractions result in the reduction of particle size (less than 1 mm) of the food as well as drug which are sent forward in the suspension form.⁸

There are at least two main targets which could be used for anchoring of delivery system through mucoadhesive in the GIT, the mucosal tissue and mucosal gel layer. The mucus layer is the first surface encountered by particulate system and its complex structure offers many opportunities for the development of adhesive interaction with small polymeric particles either through nonspecific or specific interaction between complimentary structures.⁹Gastric resident time (GRT) is a significant factor in determining medication absorption in dose form. Due to a variable and short gastric emptying interval, insufficient drug release from the drug delivery system (DDS) above the absorption zone (stomach and upper portion of small intestine) may result in reduced efficiency of the provided dosage.¹²

GRDDS are designed to increase the gastric retention time of drugs that are

1. Poorly soluble in high pH range.

2. Having a Narrow absorption window in GIT.

3. Not stable in Intestinal Environment.

4. Locally active in the stomach.¹⁰

The controlled gastric retention of solid dosage forms may be achieved by the mechanisms of mucoadhesion, flotation, sedimentation, expansion, modified shape systems, or by the simultaneous administration of pharmacological agents that delay gastric emptying. Several approaches are currently used to prolong gastric retention time.¹⁶

Fig No. 1: - Structure of Aspirin

The main objective of this present investigation was to formulate, develop and evaluate gastro-retentive sustained release alginate beads of Aspirin was prepared by the simple ionotropic gelation method, in order to minimize gastric mucosal irritation caused by the release of Aspirin by other systems.

MATERIALS AND METHODS:

Materials:

Aspirin, HPMC K4M, HPMC K15M, HPMC K100M, Sodium Alginate, AlCl₂, CaCl₂, Acetic Acid were collected from our college SSJIPER, Jamner.

Preparations of Floating Alginate Beads:

Sodium alginate and HPMC K4M, HPMC K15M, HPMC K100M dispersions of different concentrations were prepared by mixing required amount of alginate (Table 1) in 100ml of deionized water under gentle agitation. Aspirin and aluminum chloride (as crosslinking agent), calcium chloride (as gas forming agent) was dispersed in alginate dispersion under constant stirring for uniform mixing.

The dispersion was sonicated for 30 minutes to remove any air bubbles. The resultant dispersion was dropped through a 22gauge syringe needle into 100ml of 1% (w/v) calcium chloride solution containing 10% (v/v) acetic acid at room temperature. Then the beads formed were allowed to remain in the stirred solution for 10min. The beads were filtered and subsequently air dried to constant weight.¹¹

Table No: 01 Formulation Design of Floating Beads of Aspirin

Sr. No.	Ingredients	ASP1	ASP2	ASP3	ASP4	ASP5
1.	Aspirin (gm)	1	1	1	1	1
2.	HPMC K4M (gm)	1.0	1.5	---	2.0	---
3.	HPMC K15M (gm)	---	---	1.0	---	1.0
4.	HPMC K100M (gm)	---	---	---	1.0	1.5
5.	Sodium Alginate (%w/v)	3	3	3	3	3
6.	AlCl2	2	2	2	2	2
7.	CaCl2 (gm)	2	2	2	2	2
8.	Acetic Acid (%v/v)	10	10	10	10	10

Fig No. 2: - Floating Beads of Aspirin Containing Sodium Alginate and Calcium Chloride

Evaluation Parameter:

Pre-Formulation Parameter:

1) Melting point:

Melting point of Aspirin was determined by capillary fusion method.

2) Determination of Solubility:

It is an essential and extensively utilized pre-formulation parameter. The solubility of drug was determined as per BCS classification system. The solubility was checked in 250 ml different medium and water. The solubility of Aspirin in different solvents like water, 0.1 N. HCl, and phosphate buffer pH 6.8 was determined by using standard procedure.^1,13

3) Calibration Curve of Aspirin: -

Calibration curve of Aspirin was performed with the help of 0.1 N. HCl (PH 1.2) with the various concentration solution such as (0, 5, 10, 15, 20, 25 µg/ml.) at the λ max of 270nm.

Post-Formulation Parameter:

1) Particle size determination:

The particle sizes of formulations were measured by using an optical microscope fitted with an ocular and stage micrometer. In all measurements at least 100 particles were examined, and each experiment was carried out in triplicate.^4,7,11,15,18

2) Percentage Yield:

Percentage yield can be determined by calculating the initial weight of raw material and the final weight of solid dispersion. Percentage yield can be calculated by using the formula⁷

Percentage yield = Practical yield/theoretical yield × 100

3) In Vitro Buoyancy Study:

The total floating time and the floating lag time (FLG) were calculated using an in vitro buoyancy study (TFT). Five Aspirin Sustained-release floating beads were used in the study, and they were placed in 900 mL of 0.1(N) hydrochloric acid in the dissolution basket to keep the temperature at 37±0.5°C. The floating lag time is the amount of time it takes for the sodium alginate Aspirin beads to float to the top of the dissolution liquid. When the sodium alginate Aspirin beads float peacefully in the dissolution liquid, the total floating time has come to an end.^2,5,6,17

4) Swelling Study:

For swelling study, the beads were weighed and placed inside the wire basket of USP dissolution apparatus II. The basket containing beads were placed inside the beaker filled with 900ml of HCl (pH 1.2) maintained at temperature 37±0.5°C. After 12h, the beads were removed from the swelling media study and studied for swelling characteristics. Beads were studied for swelling characteristics. The beads were removed after 12 h from their media and weighed after drying the beads with filter paper. At last, the swelling index was estimated as percentage using the formula given below.^8,13,17

% Swelling index = Final wt. of beads - Initial wt. of beads / Initial wt. of beads x 100

5) Entrapment Efficiency:

Aspirin incorporation efficiency was analyzed by weighing 10mg of floating Beads then dissolved in methanol. The above solution was agitated to solubilize the drug and polymers and to extract the drug. Then solution was filtered. The drug was determined using spectrophotometer at the λ max of 270nm. The encapsulation efficiency was determined using the following equation.^{9,10,14,16,18,19}

% Drug entrapment = Calculated drug concentration/ Theoretical drug concentration × 100

6) Floating Lag Time:

In a beaker 100ml of 0.1 N. HCL was taken and 100mg of alginate beads were dropped in beaker. The stop watch was started and the time duration was noted till the beads reached the top of the fluid in the beaker.¹¹

RESULT AND DISCUSSION:

Pre-Formulation Studies:

1) Melting Point:

The melting point of Aspirin was found to be in the ranges of 120 – 136 ̊C by capillary fusion method.

2) Solubility:

Aspirin is slightly soluble in water and soluble in organic solvent like ethanol.

3) Calibration Curve of Aspirin:

The calibration curve of Aspirin shows the straight-line equation given in fig. no. 3.

Table No. 2: - Standard Calibration Curve of Aspirin

Sr. No.	Concentration (µg/ml)	Absorbance (nm.)
1.	0	0
2.	5	4.9
3.	10	9.7
4.	15	14.7
5.	20	19.6
6.	25	25

Fig No. 3: - Calibration Curve of Aspirin

Post-Formulation Parameter:

Table No. 3: Post-Formulation Parameter of Floating Beads of Aspirin

Parameters	Batches
Parameters	ASP1	ASP2	ASP3	ASP4	ASP5
Particle size determination (mm.)	2.02	1.98	1.99	1.95	2.08
Percentage Yield (%)	87.73	93.96	83.32	94.20	79.23
Swelling Index (%)	80.09	77.08	70.02	86.21	81.04
Entrapment Efficiency (%)	79.32	78.15	71.08	81.25	75.10

Table No. 4: - Buoyancy Studies

Parameters	Batches
Parameters	ASP1	ASP2	ASP3	ASP4	ASP5
In-Vitro Buoyancy Study (Sec.)	29	20	17	9	23
Total Floating Time (Hrs.)	8	9	11	8	10

1) Particle Size Analysis:

The prepared beads were analyzed by optical microscopy for their surface structure and size analysis. The surface of the prepared beads was observed under microscope for its morphological characteristics. It was found that the beads were spherical in shape. The surface of most of the beads was found to be smooth but small number of beads showed slightly rough surface within the batch. The beads were prepared using different ratios of sodium alginate and HPMC K4M to study the effect of polymer concentration on the drug release of beads and to obtain sustained release. The size of the beads was determined using calibrated stage micrometer and eyepiece micrometer. The particle size was calculated using following equation.

2) Entrapment efficiency:

The drug entrapment efficiency of all the formulations batches (ASP1-ASP5) was found to be good ranging from 71.08% to 81.25%. In case of formulation-ASP1, the percentage of encapsulation was 79.32%, In ASP4 where entrapment efficiency was 81.25%.

3) Floating/ Buoyancy lag time:

The floating lag time of all the formulations batches (ASP1-ASP5) were measured. All the formulations could float to the top in less than 1 minute.

CONCLUSION:

The aim of this study was to Formulate, Developed and Evaluate Sustained Release Floating Beads of Aspirin. It was concluded that the method of preparation of alginate beads of Aspirin was found to be simple ionotropic gelation method and it provides good yield. The floating beads of aspirin showed excellent buoyancy ability. Also floating system shows the local action on the stomach. Prepared formulation showed better sustained release behavior. Thus, Alginate can be considered as an effective carrier for the design of a gastroprotective multiarticulate drug delivery system of drugs like aspirin for the effective management of muscles aches, inflammation and headaches. Aspirin beads were concluded that the floating lag time, buoyancy is better improving their action.

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Received on 04.02.2025 Revised on 22.02.2025

Accepted on 08.03.2025 Published on 09.05.2025

Available online from May 12, 2025

Res. J. Pharma. Dosage Forms and Tech.2025; 17(2):97-101.

DOI: 10.52711/0975-4377.2025.00014

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