Optimization and In Vitro Characterization of Telmisartan Loaded Sodium Alginate Beads and Its In Vivo Efficacy Investigation in Hypertensive Induced Animal Model

Abstract

Background: Antihypertensive drug telmisartan (TEL) belongs to BCS class II, which is characterized by low water solubility and, consequently, low oral bioavailability. Gastroretentive systems may overcome the problems associated with low solubility of TEL and incomplete absorption by localizing the drug release in the stomach. The purpose of this study was to prepare TEL-loaded, oil-entrapped, floating alginate beads with the intent of enhancing the oral bioavailability of TEL for the treatment of hypertension. Methods: For the formulation and optimization of seventeen formulations of TEL-loaded oil-entrapped floating alginate beads, a central composite design was utilized. The concentration of sodium alginate (X1), the concentration of cross-linker (X2), and the concentration of sesame oil (X3) served as independent variables, whereas the entrapment efficiency (Y1), in vitro buoyancy (Y2), and drug release Q6h (Y3) served as dependent variables. Using the emulsion gelation method and calcium chloride as the cross-linking agent, different formulations of TEL alginate beads were produced. All formulations were evaluated for their entrapment efficiency percentage, in vitro buoyancy, and in vitro drug release. The optimal formulation of TEL alginate beads was prepared with and without oil and evaluated for entrapment efficiency percentage, in vitro buoyancy, swelling ratio, average size, and in vitro drug release. Using scanning electron microscopes, the surface morphology was determined. Using IR spectroscopy, the compatibility between the ingredients was determined. In vivo evaluation of the optimized formulation in comparison to the free TEL was done in hypertension-induced rats, and the systolic blood pressure and all pharmacokinetic parameters were measured. Results: The prepared beads exhibited a high entrapment efficiency percentage, in vitro buoyancy, and prolonged drug release. TEL was compatible with other ingredients, as approved by IR spectroscopy. The prepared TEL beads were spherical, as shown by the SEM. The relative bioavailability of TEL-loaded oil-entrapped beads was 222.52%, which was higher than that of the pure TEL suspension. The prepared TEL beads formulation exhibited a higher antihypertensive effect for a prolonged time compared to pure TEL suspension. Conclusions: It can be concluded that this innovative delivery method of TEL-loaded oil-entrapped beads is a promising tool for enhancing drug solubility and, thus, oral bioavailability and therapeutic efficacy, resulting in enhanced patient compliance. Furthermore, the in vivo study confirmed the formulation’s extended anti-hypertensive activity in animal models.

Expanding the Manufacturing Approaches for Gastroretentive Drug Delivery Systems with 3D Printing Technology

“…The objective of the study, which was to enhance the oral bioavailability of telmisartan by creating oil-entrapped telmisartan beads, was successfully proved by an in vivo study that confirmed an extended anti-hypertensive activity of the API. In vitro studies confirmed the in vivo results as the formulation proved to have a high entrapment efficiency percentage and remained buoyant for 7 h while showing an extended release over 12 h in a simulated gastric fluid [ 58 ]. Microporous systems are another category of multiple-unit FDDSs, obtained through the encapsulation of a drug reservoir inside a microporous compartment, presenting pores along the walls.…”

Optimization and Characterization of Sodium Alginate Beads Providing Extended Release for Antidiabetic Drugs

“…If we can dissolve solubilized nanoparticles alongside the SA matrix, the polymer erosion in the gastrointestinal tract will lead to an extended-release profile of the encapsulated drugs. With the coacervation method, we add the SA solution dropwise to the calcium ion solution, and small beads will be formed; these can be freeze-dried, providing long-term stability and excellent swelling ability, with systems that float on top of gastric juice [17,18] (Figure 1).…”

“…If we can dissolve solubilized nanoparticles alongside the SA matrix, the polymer erosion in the gastrointestinal tract will lead to an extended-release profile of the encapsulated drugs. With the coacervation method, we add the SA solution dropwise to the calcium ion solution, and small beads will be formed; these can be freeze-dried, providing long-term stability and excellent swelling ability, with systems that float on top of gastric juice [17,18] (Figure 1). This methodology provides physical encapsulation of the drugs and the nanocarrier system; however, there are alternatives where chemical conjugation would occur between This methodology provides physical encapsulation of the drugs and the nanocarrier system; however, there are alternatives where chemical conjugation would occur between the nanocarrier-forming polymer, lipid, etc., and the sodium alginate biopolymer.…”