Formulation And Evaluation of Mucoadhesive Insitu Gel for Enhanced Gastric Retention

The oral route remains the most preferred and extensively employed method of drug administration because of its convenience, non-invasive nature, safety, affordability, and better patient compliance. It accommodates a wide range of dosage forms, including tablets, capsules, and liquid preparations, and enables the development of controlled and sustained-release systems to maintain therapeutic drug concentrations over an extended period while reducing dosing frequency. However, the effectiveness of oral drug delivery may be limited by several physiological factors, such as fluctuations in gastric pH, enzymatic degradation within the gastrointestinal tract, hepatic first-pass metabolism, and variability in gastric emptying time. These factors can reduce drug bioavailability and present significant challenges during the formulation and development of oral drug delivery systems.^[1]

Gastro-retentive drug delivery systems are advanced oral formulations developed to remain in the stomach for a prolonged duration, thereby enhancing the absorption of drugs with a narrow absorption window, improving bioavailability, and providing sustained or controlled drug release in the upper gastrointestinal tract. These systems employ different mechanisms, such as floating, swelling or expanding, mucoadhesion, high-density formulations, or delayed gastric emptying, to prolong gastric residence time and retain the dosage form within the stomach. As a result, gastro-retentive systems can reduce dosing frequency, maintain consistent plasma drug concentrations, improve therapeutic effectiveness for suitable drugs, and enhance patient compliance.^[2]

Mucoadhesive drug delivery systems have gained considerable interest as advanced drug delivery approaches due to their ability to enhance drug bioavailability by increasing the residence time of the dosage form at the site of absorption and providing controlled drug release. Mucoadhesion is the phenomenon by which a dosage form or polymer adheres to the mucosal surface through interaction with the mucus layer, thereby retaining the formulation at the target site for an extended period. Various mucoadhesive dosage forms, including tablets, microspheres, patches, films, and in-situ gels, are designed to attach to mucosal tissues such as the gastric mucosa. This prolonged retention facilitates sustained drug release and may improve drug absorption and bioavailability by maintaining close contact with the absorptive surface.^[3]

Type 2 diabetes mellitus is a long-term metabolic disorder characterized by insulin resistance, in which peripheral tissues exhibit a reduced response to insulin, often accompanied by impaired insulin secretion. These abnormalities result in persistent hyperglycaemia and disrupted glucose metabolism. If left inadequately controlled, the disease may lead to severe complications, including cardiovascular disorders, diabetic nephropathy, neuropathy, retinopathy, and other systemic complications. Effective management of type 2 diabetes mellitus requires adequate glycaemic control through lifestyle modifications along with appropriate pharmacological therapy, including oral antidiabetic agents and insulin, to minimize the risk of disease progression and associated complications.^[4]

In-situ gel systems are liquid formulations that undergo sol–gel transition upon exposure to physiological conditions such as pH, temperature, or ionic strength. The incorporation of mucoadhesive polymers into these formulations enables the system to adhere to mucosal surfaces, thereby enhancing the residence time and bioavailability of the drug. Upon administration, the system transforms into a gel that remains at the site of application, providing sustained and controlled drug release.^[5]

Pioglitazone Hydrochloride (HCl) is an oral antidiabetic agent belonging to the thiazolidinedione class, used in the management of Type II Diabetes Mellitus. It works by enhancing insulin sensitivity in peripheral tissues such as skeletal muscle, adipose tissue, and the liver, without stimulating insulin secretion. Pioglitazone activates peroxisome proliferator-activated receptor gamma (PPAR-γ), leading to improved glucose uptake and utilization. It has a relatively intermediate elimination half-life, ranging from 3 to 7 hours.^[6.7]

The basic idea behind the development of such a system is to maintain a constant level of drug in the gastrointestinal tract for action, The drug usually keeps mucoadhesive in the gastric fluid and slowly dissolves at a pre-determined rate to release the drug slowly from the dosage form.

Hence aim of this study is to formulation and evaluation of Mucoadhesive In-situ gel of Pioglitazone HCl for enhanced gastric retention to improve patient compliance.

MATERIALS AND METHOD:

sodium alginate from rolex chemical industries Mumbai, gum tragacanth from loba chemie pvt.ltd Mumbai, sodium bicarbonate from qualigens fine chemicals Mumbai, calcium carbonate from s d fine-chemical Ltd Mumbai, trisodium citrate from Loba Chemie Pvt. Ltd. Mumbai, all the chemicals were used for in-situ gel preparation.

PREFORMULATION STUDIES: ^[8,11]

Determination of melting point of the drug

The melting point of Pioglitazone HCl determined using the capillary tube method with the aid of a melting point apparatus.

Determination of absorption maximum (λmax) of the drug

A solution of Pioglitazone HCl with a concentration of 10 µg/mL was prepared using0.1N HCl. The prepared solution was scanned in the wavelength range of 200–400 nm using a UV-Visible spectrophotometer to determine the wavelength of maximum absorption (λmax). The absorption spectrum obtained was used to identify the λmax of Pioglitazone HCl.

Fourier transform infrared spectroscopy (FTIR) studies

FTIR studies were carried out to investigate the compatibility between Pioglitazone HCl and the selected excipients. The infrared spectra of pure Pioglitazone HCl and its physical mixtures with sodium alginate, gum tragacanth, trisodium citrate, sodium bicarbonate, calcium carbonate were recorded over a spectral range of 650–4500 cm⁻¹using a Shimadzu IR Spirit FTIR spectrophotometer.

Standard calibration curve of Pioglitazone HCl

Calibration curve was constructed by using 0.1N HCl 100 mg accurately weighed metronidazole was dissolved in 0.1N HCl and the volume is made up to 100ml with 0.1N HCl and filtered using Whatman filter paper and solution was used as standard solution.

• 100 mg of drug was dissolved in 100 ml of 0.1N HCl in a standard volumetric flask.
• 10 ml of the above solution was diluted to 100 ml using 0.1 N HCl and used as working stock solution.
• From the above solution 6, 12, 18, 24 and 30μg/ml UV spectrophotometer at λ max 269nm.
• Calibration curve was plotted between concentration and absorbance and r² value of this graph was calculated to check the linearity of the absorbance against concentration.

METHOD^[12]

Ion activated method

In around 75% water, measured quantity of Sodium alginate required to make a solution was dissolved in distilled water at 60℃ using heating magnetic stirrer. After cooling to below 40℃, appropriate amounts of polymer Trisodium citrate. The drug was dissolved in appropriate solvent long with gas generating agents (Calcium carbonate or Sodium bicarbonate), Gum tragacanth were dissolved uniformly into Sodium alginate solution with continuous stirring the stirring was continued after complete addition until uniform dispersion was obtained and dispersion was allowed to cool at room temperature. Finally, the volume was adjusted to 100% with distilled water and the mixture was mixed well to get final preparation which was stored in amber colour bottle

COMPOSITION OF MUCOADHESIVE ORAL IN-SITU GEL FORMULATIONS

 

 

Fig 1: λ max of Pioglitazone HCl

 

 

Figure 2: Standard calibration curve of Pioglitazone HCl

 

 

Figure 3: FT-IR Spectra of Pioglitazone HCl

 

 

Figure 4: FTIR spectrum of drug and polymers mixture.

 

 

Figure 5: Drug content

 

 

Figure 6: pH

 

 

Figure 7: Cumulative drug release profile

CONCLUSION

The present study successfully formulated and evaluated Pioglitazone Hydrochloride gastro-retentive mucoadhesive In-situ gel by the ion-activated gelation method. The prepared formulations exhibited satisfactory physicochemical characteristics, including acceptable drug content, suitable pH, rapid floating with a floating lag time, and floating duration. The formulations also demonstrated sustained in vitro drug release, indicating their suitability for gastro-retentive drug delivery. The optimized formulation provided prolonged drug release, ensuring sustained therapeutic effect. Hence, the developed gastro-retentive In-situ gel of Pioglitazone Hydrochloride can be considered a promising oral drug delivery system for improving gastric retention, sustaining drug release, enhancing bioavailability, in the management of Type 2 diabetes mellitus.

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