Formulation Strategies in Medicinal Chemistry: Enhancing Bioavailability

Bonan Sherwood^*
*Correspondence: Bonan Sherwood, Department of Drug Design and Development (CD3), KU Leuven R&D, Waaistraat, Leuven, Belgium, Email:

Introduction

Bioavailability, defined as the proportion of an orally administered drug that reaches the systemic circulation in its active form, is a critical parameter in the design and development of therapeutic agents. Poor bioavailability is one of the most significant challenges in the field of medicinal chemistry and drug development, as it can lead to ineffective therapies, increased side effects and suboptimal dosing regimens. The ability to enhance bioavailability is essential for improving the therapeutic outcomes of drugs, reducing the need for high doses and ensuring better patient compliance. Medicinal chemists and pharmaceutical scientists have developed a variety of strategies to improve the bioavailability of drugs, especially for compounds with poor solubility or permeability. These strategies not only address the challenges posed by the physicochemical properties of drugs but also consider the complex biological processes involved in drug Absorption, Distribution, Metabolism and Excretion (ADME). This introduction sets the stage for exploring these formulation strategies and their application in overcoming the limitations posed by bioavailability in medicinal chemistry. In the following sections, we will examine the key formulation strategies, discuss their mechanisms and evaluate their impact on drug efficacy, safety and patient outcomes [1].

Description

Bioavailability is a critical factor in the effectiveness of oral drugs, determining the fraction of the administered dose that reaches the systemic circulation in its active form. Many drug candidates, especially those with poor solubility, low permeability, or extensive first-pass metabolism, face significant bioavailability challenges that can compromise therapeutic efficacy. This review explores various formulation strategies developed in medicinal chemistry to enhance drug bioavailability. Approaches such as lipid-based formulations, solid dispersions, prodrugs and the use of excipients to improve solubility and permeability are discussed in detail. Additionally, emerging technologies like nanomedicine and controlled-release systems, which offer solutions for overcoming biological barriers, are highlighted. The role of nanocarriers, including liposomes and solid lipid nanoparticles, in improving drug delivery and targeting is also examined. While these strategies address issues of solubility, permeability and metabolism, a multifaceted approach is often required for optimal bioavailability. It refers to the fraction of an administered dose of a drug that reaches the bloodstream in its active form and it plays a pivotal role in the drug's therapeutic effectiveness. This is often due to factors such as poor solubility, low permeability and extensive first-pass metabolism. Medicinal chemistry, in its ongoing efforts to improve drug design, focuses on strategies that can enhance bioavailability, ensuring that drugs can exert their intended therapeutic effects at the desired sites in the body [2].

When a drug is administered orally, it first must dissolve in the Gastrointestinal (GI) tract. Once dissolved, the drug must pass through the intestinal membrane to enter the bloodstream and subsequently circulate throughout the body. However, many drugs face substantial challenges in this process, primarily related to solubility and permeability. Poor solubility means that the drug cannot be adequately dissolved and absorbed in the GI tract, resulting in a reduced amount of the active compound reaching systemic circulation. Many drug candidates, especially those developed in the early stages of pharmaceutical research; suffer from low aqueous solubility, which limits their absorption. A number of formulation strategies have been developed to address this issue, such as the use of solubility-enhancing excipients and the development of lipid-based formulations. Another challenge that often hinders bioavailability is the permeability of drugs across the intestinal wall. The drug must cross the epithelial cell layer lining the intestine, a process that can be complicated by factors such as the size and charge of the molecule, as well as the presence of efflux pumps that actively remove compounds from the cells. In this regard, a variety of strategies have been explored to enhance permeability. Nanoparticles and lipid-based formulations have also been studied for their ability to improve permeability. These approaches allow drugs to bypass the efflux pumps and cross the intestinal membrane more efficiently, increasing their bioavailability [3].

Furthermore, a significant issue with bioavailability is the first-pass metabolism that occurs after a drug is absorbed into the bloodstream via the GI tract. Once absorbed, the drug is often transported to the liver via the portal circulation. The liver metabolizes many drugs through enzymes such as cytochrome P450 and this first-pass metabolism can lead to significant degradation of the drug before it reaches systemic circulation. One strategy to address this issue is the development of prodrugs, which are chemically modified compounds designed to overcome the challenges of first-pass metabolism. Prodrugs are typically inactive or less active until they undergo metabolic conversion in the body, where they are transformed into their active form. This approach helps improve the bioavailability of drugs by allowing them to bypass or minimize the impact of first-pass metabolism. The complexity of drug absorption and metabolism means that no single formulation strategy is universally effective. A multifaceted approach, often involving the combination of several strategies, is typically necessary to enhance bioavailability. The small size of nanoparticles also allows for enhanced cellular uptake, which can improve drug absorption. Furthermore, the surface properties of nanoparticles can be modified to target specific tissues or cells, providing a more controlled and efficient drug delivery system. Nano carriers can also be used to bypass barriers such as the blood-brain barrier, which often hinders the delivery of drugs to the central nervous system [4].

Another innovative approach that has emerged is the use of biologics, such as monoclonal antibodies, peptides and vaccines, to treat diseases. These biologics typically face significant bioavailability challenges because of their large molecular size, instability in the GI tract and poor permeability across cellular membranes. As a result, biologics are usually administered via injection or infusion, bypassing the GI tract altogether. However, significant efforts are being made to develop oral formulations of biologics. These strategies include encapsulating biologics in nanoparticles or using enzyme inhibitors to protect them from degradation in the GI tract. The aim is to develop oral delivery systems for biologics that could provide the convenience of oral administration without compromising efficacy. Ultimately, improving bioavailability is not just about enhancing the drug’s absorption and stability; it also involves optimizing the overall drug development process to ensure that the drug reaches its intended target at the appropriate time and concentration. The interplay of pharmacokinetics and pharmacodynamics how the body absorbs, distributes, metabolizes and eliminates the drug and how the drug interacts with its target receptors needs to be understood to tailor formulation strategies appropriately. Moreover, the choice of formulation must take into account patient factors, including age, health status and other medications being taken, to ensure the drug is both effective and safe [5].

Conclusion

In conclusion, improving the bioavailability of drugs is an essential aspect of drug development and various formulation strategies are being explored to overcome the challenges of solubility, permeability and first-pass metabolism. From prodrugs and lipid-based formulations to nanotechnology and controlledrelease systems, these approaches offer promising solutions to improve the therapeutic efficacy of drugs. As our understanding of bioavailability and drug delivery continues to grow, it is likely that more innovative strategies will emerge to optimize drug absorption, minimize side effects and enhance patient outcomes, ultimately leading to safer and more effective therapies.

Acknowledgment

None.

Conflict of Interest

None.

References

1. Kumar, Sunil, Kamalinder K. Singh and Rekha Rao. "Enhanced anti-psoriatic efficacy and regulation of oxidative stress of a novel topical babchi oil (Psoralea corylifolia) cyclodextrin-based nanogel in a mouse tail model." J Microencapsul 36 (2019): 140-155.

   Google Scholar, Crossref, Indexed at

2. Mishra, Dinesh Kumar, Vinod Dhote, Arpit Bhargava and Dinesh Kumar Jain, et al. "Amorphous solid dispersion technique for improved drug delivery: Basics to clinical applications." Drug Deliv Transl Res 5 (2015): 552-565.

   Google Scholar, Crossref, Indexed at

3. Lu, Cheng, Yi Lu, Jian Chen and Wentong Zhang, et al. "Synchronized and sustained release of multiple components in silymarin from erodible glyceryl monostearate matrix system." Eur J Pharm Biopharm 66 (2007): 210-219.

   Google Scholar, Crossref, Indexed at

4. Marciello, Marzia, Silvia Rossi, Carla Caramella and Carmen Remunan-Lopez. "Freeze-dried cylinders carrying chitosan nanoparticles for vaginal peptide delivery." Carbohydr Polym 170 (2017): 43-51.

   Google Scholar, Crossref, Indexed at

5. Kanimozhi, Perumal and Nagarajan Rajendra Prasad. "Antioxidant potential of sesamol and its role on radiation-induced DNA damage in whole-body irradiated Swiss albino mice." Environ Toxicol Pharmacol 28 (2009): 192-197.

   Google Scholar, Crossref, Indexed at