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Induction of drug-metabolizing enzymes and efflux transporters (DMET) through activation of pregnane x receptor (PXR) is the primary factor involved in almost all bioavailability and drug resistance-related problems of anticancer drugs. PXR is a transcriptional regulator of many metabolizing enzymes and efflux transporters proteins like p-glycoprotein (p-gp), multidrug resistant protein 1 and 2 (MRP 1 and 2), and breast cancer resistant protein (BCRP), etc. Several anticancer drugs are potent activators of PXR receptors and can modulate the gene expression of DMET proteins. Involvement of anticancer drugs in transcriptional regulation of DMET can prompt increased metabolism and efflux of their own or other co-administered drugs, which leads to poor site-specific bioavailability and increased drug resistance. In this review, we have discussed several novel strategies to evade drug-induced PXR activation and p-gp efflux including assessment of PXR ligand and p-gp substrate at early stages of drug discovery. Additionally, we have critically discussed the chemical structure and drug delivery-based approaches to avoid PXR binding and inhibit the p-gp activity of the drugs at their target sites.

The presence of impurities is the primary cause of safety related drug product recall. Clinical data generated during the drug discovery process may not be able to conclude the long-term safety of a drug. The best way to ensure drug safety is to control the associated impurities. It can be achieved by a clear understanding of the route and factors for impurity formation. Tight control on manufacturing, storage, and transport process can provide a beneficial effect on minimization of impurity generation. Control strategies employing quality by design and risk assessment-based approaches potentially enhance drug safety profile and, thereby, minimize product recalls. Prior understanding of key aspects of the safety profile of impurities, post-marketing surveillance criticalities, and establishment of constructive preventive strategies is the best way to minimize unwanted product recall due to associated safety issues. Effective preventive strategies should be designed and executed during the product manufacturing and supply chain process. The novelty of this article can be justified by the unavailability of any similar type of reports discussing the functional pathway of regulatory bodies aiming for effective control of drug impurities. This article contains novel, critical, and constructive prevention strategies to establish a robust safety profile of pharmaceutical products.

Electrospun technology becomes a valuable means of fabricating functional polymeric nanofibers with distinctive morphological properties for drug delivery applications. Nanofibers are prepared from the polymer solution, which allows the direct incorporation of therapeutics such as small drug molecules, genes, and proteins by merely mixing them into the polymeric solution. Due to their biocompatibility, adhesiveness, sterility, and efficiency in delivering diverse cargoes, electrospun nanofibers have gained much attention. This review discusses the capabilities of the electrospun nanofibers in delivering different therapeutics like small molecules, genes, and proteins to their desired target site for treating various ailments. The potential of nanofibers in administering through multiple administration routes and the associated challenges has also been expounded along with a cross-talk about the commercial products of nanofibers for biomedical applications.

Globally, diabetic nephropathy (DN) is the foremost cause of end-stage renal disease. With the incidence of diabetes increasing day by day, DN's occurrence is expected to surge to pandemic proportions. Current available therapeutic interventions associated with DN emphasize blood pressure, glycemia and lipid control while ignoring DN's progression mechanism at a molecular level. This review sheds light on the molecular insights involved in DN to help understand the initiation and progression pattern. Further, we summarize novel strategies with reported applications in developing a nanomedicine-based platform for DN-targeted drug delivery to improve drug efficacy and safety.

Success of a drug discovery program is highly dependent on rapid scientific advancement and periodic inclusion of sensitive and specific analytical techniques. Biological membrane transporters can significantly alter the bioavailability of a molecule in its actual site of action. Expression of transporter proteins responsible for drug transport is extremely low in the biological system. Therefore, proper scientific planning in selection of their quantitative analytical technique is essential. This article discusses critical advancement in the analytical strategies for quantification of clinically relevant biological transporters for the drugs. Article cross-talked key planning and execution strategies concerning analytical quantification of the transporters during drug discovery programs.

Nanomedicines refers to nanotechnology inspired pharmaceutical products often referred to as 'nanopharmaceuticals.' It has displayed commendable potential in enhancing therapeutic efficacy as well as in reducing the side effects associated with conventional drug counterpart. Recent years have monitored the entry of a large amount of nanomedicine in the market with an appreciable market share to date. Despite this, the development of nanomedicine is posing challenges (i.e., safety, regulatory hurdles, cost, scale-up issues, etc.) that need to be resolved for their market entry. This review presents a cross-sectional discussion on the nanomedicine-derived products available in the market for both clinical and diagnostic applications. An overview of its market potential, market size, and the products that are currently in the clinical stages is also provided. The review also expounds on the challenges faced by nano-drug products at the time of their commercialization.

Highlights • Artificial Intelligence (AI) has revolutionized many aspects of the pharmaceuticals. • AI assistance to pharma industries helps to improve overall life cycle of product. • AI can be implemented in pharma ranging from drug discovery to product management. • Future challenges related to AI and their respective solutions have been expounded., Artificial Intelligence (AI) has recently started to gear-up its application in various sectors of the society with the pharmaceutical industry as a front-runner beneficiary. This review highlights the impactful use of AI in diverse areas of the pharmaceutical sectors viz., drug discovery and development, drug repurposing, improving pharmaceutical productivity, clinical trials, etc. to name a few, thus reducing the human workload as well as achieving targets in a short period. Crosstalk on the tools and techniques utilized in enforcing AI, ongoing challenges, and ways to overcome them, along with the future of AI in the pharmaceutical industry, is also discussed., Teaser Artificial intelligence-integrated drug discovery and development has accelerated the growth of the pharmaceutical sector, leading to a revolutionary change in the pharma industry. Here, we discuss areas of integration, tools, and techniques utilized in enforcing AI, ongoing challenges, and ways to overcome them.

Recent findings suggest that the cellular and extracellular materials surrounding the cancerous cells from an atypical tumor microenvironment (TM) play a pivotal role in the process of tumor initiation and progression. TM comprises an intricate system involving diverse cell types including endothelial cells, pericytes, smooth muscle cells, fibroblasts, various inflammatory cells, dendritic cells, and cancer stem cells (CSCs). The TM-forming cells dynamically interact with the cancerous cells through various signaling mechanisms and pathways. The existence of this dynamic cellular communication is responsible for creating an environment suitable for sustaining a reasonably high cellular proliferation. Presently, researchers are showing interest to use these TM conditions to mediate effective targeting measures for cancer therapy. The use of nanotherapeutics-based combination therapy; stimuli-responsive nanotherapeutics targeting acidic pH, hypoxic environment; and nanoparticle-induced hyperthermia are some of the approaches that are under intense investigation for cancer therapy. This review discusses TM and its role in cancer progression and crosstalk understanding, opportunities, and epigenetic modifications involved therein to materialize the capability of nanotherapeutics to target cancer by availing TM. STATEMENT OF SIGNIFICANCE: This article presents various recent reports, proof-of-concept studies, patents, and clinical trials on the concept of tumor microenvironment for mediating the cancer-specific delivery of nanotechnology-based systems bearing anticancer drug and diagnostics. We highlight the potential of tumor microenvironment; its role in disease progression, opportunities, challenges, and allied treatment strategies for effective cancer therapy by conceptual understanding of tumor microenvironment and epigenetic modifications involved. Specifically, nanoparticle-based approaches to target various processes related to tumor microenvironment (pH responsive, hypoxic environment responsive, targeting of specific cells involved in tumor microenvironment, etc.) are dealt in detail.

Preparation of the biological samples is one of the most critical steps in sample analysis. In past decades, the liquid-liquid extraction technique has been used to extract the desired analytes from complex biological matrices. However, solid-phase extraction (SPE) gained popularity due to versatility, simplicity, selectivity, reproducibility, high sample recovery %, solvent economy, and time-saving nature. The superior extraction efficiency of SPE can be attributed to the development of advanced techniques, including the nanosorbents technology. The nanosorbent technology significantly simplified the sample preparation, improved the selectivity, diversified the application, and accelerated the sample analysis. This review critically expands on the to-date advancements reported in SPE with particular regards to the nanosorbent technology.

Background Prostate cancer (PC) has the highest prevalence in men and accounts for a high rate of neoplasia-related death. Doxorubicin (DOX) is one of the most widely used anti-neoplastic drugs for prostate cancer among others. However, it has low specificity and many side effects and affects normal cells. More recently, there have been newly developed drug delivery tools which are graphene or graphene-based, used to increase the specificity of the delivered drug molecules. The graphene derivatives possess both π-π stacking and increased hydrophobicity, factors that increase the likelihood of drug delivery. Despite this, the hydrophilicity of graphene remains problematic, as it induced problems with stability. For this reason, the use of a chitosan coating remains one way to modify the surface features of graphene. Method In this investigation, a hybrid nanoparticle that consisted of a DOX-loaded reduced graphene oxide that is stabilized with chitosan (rGOD-HNP) was developed. Result The newly developed rGOD-HNP demonstrated high biocompatibility and efficiency in entrapping DOX (~65%) and releasing it in a controlled manner (~50% release in 48 h). Furthermore, it was also demonstrated that rGOD-HNP can intracellularly deliver DOX and more specifically in PC-3 prostate cancer cells. Conclusion This delivery tool offers a feasible and viable method to deliver DOX photo-thermally in the treatment of prostate cancer.

Adenosine receptors (ARs) are classified as A1, A2A, A2B, and A3 subtypes belonging to the superfamily of G-protein-coupled receptors (GPCRs). Several molecular modeling approaches have been developed for A2BAR and its antagonists, from the construction of a homology model, molecular docking, molecular dynamics (MD) simulations, and 3D quantitative structure-activity relationship (QSAR) modeling to pharmacophore modeling, each of which has different objectives and outcomes. In this review, we provide a systematic outline of advances in molecular modeling approaches towards A2BAR for deducing its structure and interactions with various types of antagonist. The information, methods and perspectives presented here provides impetus for medicinal chemists to discover potential ligands that can bind selectively with higher affinity to A2BAR.

Neuropathic pain (NeP) is a complex chronic pain condition associated with nerve injury. Approximately, 7-10% of the general population across the globe is suffering from this traumatic condition, but the existing treatment strategies are inadequate to deliver pain relief and are associated with severe adverse effects. To overcome these limitations, lot of research is focussed on developing new molecules with high potency and fewer side effects, novel cell and gene-based therapies and modification of the previously approved drugs by different formulation aspects. Nanomedicine has attracted a lot of attention in the treatment of many diverse pathological conditions because of their unique physiochemical and biological properties. In this manuscript, we highlighted the emerging role of nanomedicine in different therapies (drug, cell and gene), also we emphasised on the challenges associated with nanomedicine such as development of well-characterised nanoformulation, scaling of batches with reproducible results and toxicity along with this we discussed about the future of nanomedicine in the treatment of neuropathic pain.

In tumorous tissues, the absence of vasculature supportive tissues intimates the formation of leaky vessels and pores (100 nm to 2 μm in diameter) and the poor lymphatic system offers great opportunity to treat cancer and the phenomenon is known as Enhanced permeability and retention (EPR) effect. The trends in treating cancer by making use of EPR effect is increasing day by day and generate multitudes of possibility to design novel anticancer therapeutics. This review aimed to present various factors affecting the EPR effect along with important things to know about EPR effect such as tumor perfusion, lymphatic function, interstitial penetration, vascular permeability, nanoparticle retention etc. This manuscript expounds the current advances and cross-talks the developments made in the of EPR effect-based therapeutics in cancer therapy along with a transactional view of its current clinical and industrial aspects.

Neurodegenerative diseases are complex in both their nature and prognosis. The difficulties associated with penetrating the blood-brain barrier (BBB), achieving site-specific targeting to the brain, and identifying the genetic etiologies responsible make treating neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and stroke, challenging. The aim to treat disease at the molecular level has galvanized nanotechnology research. Among the forms of nanoparticles (NPs) explored thus far, nanodiamonds (NDs) have shown great potential. Their unique physicochemical properties, such as a nanometer size range, stable and inert core, tunable surface, intrinsic fluorescence without photobleaching, negligible toxicity, and the ability to form complexes with drugs, highlight their theranostic potential. The ability of NDs to penetrate the BBB and target specific affected areas of the brain could take research one step closer to understanding the underlying disease etiology and unlocking more efficient methods of delivering neuromedicine to specific areas of the brain. Here, we explore interactions between NDs and the neuronal circuitry with a focus on the therapeutic potential of NDs as treatments for neurodegenerative diseases.

Advancement in metabolism profiling approaches and bioanalytical techniques has been revolutionized over the last two decades. Different in vitro and in vivo approaches along with advanced bioanalytical techniques are enabling the accurate qualitative and quantitative analysis of metabolites. This review summarizes various modern in vitro and in vivo approaches for executing metabolism studies with special emphasis on the recent advancement in the field. Advanced bioanalytical techniques, which can be employed in metabolism studies, have been discussed suggesting their particular application based on specific study objectives. This article can efficiently guide the researchers to scientifically plan metabolism studies and their bioanalysis during drug development programs taking advantage of a detailed understanding of instances of failure in the past.

Biosimilars are the biological product clinically identical to a biologic reference standard regarding their strength, purity, and safety. A large segment of biosimilars has been developed for the treatment of cancer. This review aims to discuss various facets of biosimilars and explicates on biosimilars accessible in the market for cancer clinical intervention. It also illustrates the outcomes of recent clinical trial studies concerning biosimilars. Further, it also crosstalk the safety profiles, regulatory approval requirements, and allied challenges therein. The work will be of significant interest to researchers working in the field of biologics and biosimilars.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease that causes swelling, redness, and arthralgia of multiple joints. Despite significant research and development on the treatment modalities for RA, there is still no established effective treatment option for eradicating joint damage and inflammation. In recent years, photothermal therapy (PTT) has emerged as a practical approach to treat RA. In this review, we outline various factors that affect the effective treatment of RA. Moreover, we discuss various PTT-based nanomaterials that can be used to treat RA.

MicroRNAs (miRNA) is vital for gene expression regulation and normal kidney function. Mainly, miRNA-30a is responsible for the homeostasis of podocytes. In the diabetic nephropathic condition, miRNA-30a is directly and primarily suppressed by hyperglycemic kidney induced Notch signaling pathway leads to podocyte damage and apoptosis. Thus, transferring the exogenous miRNA-30a to podocytes might improve albuminuria as well as podocytes injury. The deprived stability, poor targetability, and low specificity in vivo are critical limitations to attain this objective. This investigation reports the specific and efficient delivery of miRNA-30a mimic via cyclo(RGDfC)-gated polymeric-nanoplexes with dendrimer templates to alleviate podocyte conditions. The nanoplexes able to protect RNase enzyme and to exhibit greater cellular uptake viaαvβ3 receptor selective binding in HG treated podocytes. The nanoplexes up-regulated the expression level of miRNA-30a and repress the elevated Notch-1 signaling in HG exposed podocytes. The critical results of in vivo experimentation attribute marked suppression of Notch-1 in streptozotocin (STZ) induced diabetic C57BL/6 mice and reduced glomerular expansion and fibrosis in the glomerular area. Developed nanoplexes represents an efficient platform for the targeted delivery of exogenous miRNA to podocytes. The approach developed herein could be extrapolated to other gene therapeutics and other kidney-related diseases.

The circadian clock participates in various biological activities like hormone excretion, body temperature control, sleep–wake cycle, cardiac arrhythmias, and glucose homeostasis. The circadian clock is the foremost controller of metabolism. It plays a vital role in determining the summary of the bidirectional response of circadian rhythm on both energy balance and metabolic activities. Several factors affect circadian rhythms, for instance, molecular clock, physical movement, metabolic regulation, and various synchronizers. This chapter discusses various synchronizers (e.g., light, arousal stimuli, time-restricted feeding, temperature, chemical factors, mechanical stimuli, oxidative stress, chronic centrifugation, and serum shock) that play a crucial role in synchronizing the circadian rhythm. Further, it also envisaged monitoring of circadian rhythm along with detecting techniques and influence of circadian rhythms on the pharmacokinetics of the drugs.

Positron emission tomography (PET) principally relies on the physical properties of employed radioactive isotopes, for instance, fluorine-18 (18F), oxygen-15 (15O), and carbon-11 (11C). PET imaging generally works on the principle of detecting high-energy twofold-coincident photons emitting through the positron-emitting radioisotope. It provides exceptional PET imaging aptitudes with great sensitivity and accuracy of the radiotracer (in vivo). It allows three-dimensional mapping of radiopharmaceuticals, for instance, 18F-fluorodeoxyglucose. In the present scenario, PET imaging is an essential clinical modality for applications in various fields such as cancer, heart-related disorders, and neurodegenerative diseases, especially for examining murine and several small-animal models. PET is also associated with imaging challenges, such as integration amid magnetic resonance imaging and X-ray-computed tomography, the quantitative precision and accuracy, and primary adjustments amid resolution and noise. This chapter gives an insight into the basic principle of PET along with its instrumentation. The pharmacokinetics of drugs with PET as well as static and dynamic PET acquisition is also discussed.

Pharmacokinetics (PK) plays an essential role in defining the performance of a drug in the body. Hence it is vital to characterize the drug for parameters such as solubility, pKa, and log P, affecting the PK at an early drug discovery stage. However, many molecules in the hit identification and lead identification stage of discovery make the complete PK characterization incredibly difficult. The use of computational software to calculate the drug’s physicochemical properties from its structure and predict its PK is a valuable asset during drug discovery. This chapter discusses the application of computational PK in drug discovery and its potential application in personalized medicine.

Pharmacogenomics deals with the study of the variation of the DNA and RNA with the drug response. DNA polymorphisms play a vital role in the encoding of genes. Several cytochrome P450 (CYP) enzymes (e.g., CYP2D6, CYP1A2, CYP2C9, CYP2C19, and CYP3A4) are produced in the body, which has a significant influence on the metabolism of the drug in a patient when the drug is administered. For instance, two enzymes, CYP2C9 and CYP2C19, are responsible for metabolizing several crucial drugs, extremely important for clinical purposes. However, interindividual variations in drug metabolism have a huge impact and may result in a variation in drug reactions. Further, this significantly influences the efficiency and potency of drugs. This chapter provides deep insight into the effect of genetic variation in CYP enzyme metabolism and their clinical application. Further, it explains polymorphisms in the drug transporter genes.

Organ-on-a-chip (OOAC) is a recently emerging microfluidic-based device that can estimate the clinical outcome of tested drugs with a more physiologically based relevant model compared to that of two-dimensional in vitro cell model and animal studies. This reduces the drug failures at the later stages of development and thereby is cost-effective. Critical components of microfluidic devices include microfluidics, living cell tissues, stimulation, and sensing components. Microfluidic components allow the control of the flow rates of the medium to simulate the physiologic conditions and living tissue cells that comprise the suitable cells mimicking the specific organ function. Sensors allow the detection of certain nutrients and calculate the change in pH. They all regulate and collectively work to maintain the physiological microenvironment in the microfluidic device. The various OOAC-based platforms, for instance, lung-on-a-chip, are utilized to predict cytotoxicity and metabolism of drugs which are highly toxic to the liver. Lung-on-a-chip mimic the chronic lung infection, skin-on-a-chip facilitate testing of cosmetic and irritant compounds. A vascularized OOAC that can predict the absorption, distribution, metabolism, and excretion properties of the drug has also been described. The models for in vitro and in vivo correlation have also been discussed herein.

The term “organ failure” refers to the situation in the body when a particular organ loses its ability to perform its desired function. Drug-dosing errors are often encountered in patients with organ system/s failure, leading to adverse effects. The dose of a drug or the dosage regimen needs to be altered based upon the body conditions. The dose adjustment becomes even more critical in the case of organ system failure. The dose reductions or lengthening of dosing interval are carried out to maintain the dose adjustment. This chapter gives an overview of drug dose adjustment in different organ failures.

An active substance can be a worthy lead compound in the discovery of novel compounds. However, most of them may face several shortcomings, such as complicated structures, deprived solubility, and reduced stability. Hence, these compounds demand structural modification to foster novel compounds possessing some desired qualities. Structural modification of a compound is a good tactic in drug discovery and its development. Pharmacokinetic parameters of a compound can be altered by different approaches such as modifying the structure of the lead molecule, changing an ionizable group, optimizing lipophilicity, and the isosteric substitution of polar groups, synthesizing prodrugs. Regardless of few restrictions, these vital modifications in the lead compound (e.g., semisynthetic alteration or structural–activity relationship–based modification) can results in great discovery in novel drug delivery in the therapy of many diseases, for example, in malaria, diabetes, infections, cancers, and Parkinson’s disease.

Biopharmaceutics and pharmacokinetics (PK) in the discovery of drugs and their development have mesmerized scientists enormously in the last few years because researchers from both fields (i.e., medical and pharmaceuticals) have identified their immense aptitude toward the efficient designing of formulations. Both biopharmaceutics and PK are essential to enhance the results of drug therapies that can support drug product development and the determining of PK–pharmacodynamics models. Further, they also help in the establishment of in vitro–in vivo correlations of the drug. Pharmaceutical scientists need to be thorough with the basics of PK and be aware of the innovations in this field to improve the efficiency of the drug discovery process. This chapter deals in detail with the various innovations that currently rule this field.

In novel drug delivery systems (DDS), various approaches are being investigated to enhance absorption and the disposition of various kinds of drugs, whether they are hydrophilic or lipophilic. Pharmacokinetics (PK) models allow the analysis of different PK parameters to understand in vivo aspects of various complex DDS. PK modeling can play a crucial role in designing and fabricating novel drug carrier systems (e.g., liposomes, prolonged-release nanoformulations, various drug conjugates, and modified proteins) with improved PK characteristics. This chapter provides an insight into various PK parameters after intravenous (IV) bolus, IV infusion, and extravascular administration of DDS using different PK models such as compartment models (e.g., central compartment or peripheral compartment), noncompartmental analysis, and physiologic models.

Advancement in combinatorial chemistry in recent decades has synthesized a large number of potential candidates for therapeutic use. High-throughput screening technology helps select the most suitable candidate to proceed from preclinical to clinical stage. However, attrition of drug candidates at the late stage of the clinical trial is not rare. Such attrition increases drug development costs and adversely affects the demand and expectation for new therapeutic agents. Therefore decision-making step for “go or no-go” in every stage of preclinical and clinical development is of utmost importance. Pharmacokinetic (PK) characterization of the drug candidate under development is one of the essential steps that help the decision-making process. In general, PK characterization in a preclinical study assesses the drug’s absorption, distribution, metabolism and elimination (ADME) to predict its bioavailability and determine human dose. Apart from ADME assessment, drug–drug interaction, food–drug interaction, and dose modification in special population groups are evaluated by PK characterization in the clinical phase. Evaluation of the drug’s safety and efficacy is another objective of the different drug development stages, strongly correlated with PK characterization. Nowadays, PK/pharmacodynamics-based modeling, population-based PK, and physiological-based PK modeling are well adopted by industries and regulatory bodies to predict different PK parameters using an integrated experimental data approach in silico modeling. This chapter holds an extensive account of PK characterization at different drug development stages, starting from preclinical to phase III clinical trials. Several aspects of PK-based modeling have also been discussed in this chapter. The reader can get a complete understanding of the PK feature’s characterization and its application throughout a drug development process.

In humans, inflammation or exposure to exogenous stimuli in the form of an invasion by pathogenic microorganisms induces a febrile state associated and accompanied by numerous physiologic alterations, several of which have the potential to influence the pharmacokinetics (PK) of externally administered drugs. Febrile subjects may differ from afebrile subjects in how they respond to certain drugs. The intensity and extent of PK alterations may vary depending upon an invading microorganism or a bacterial toxin. Despite its significant importance in managing patients with febrile illnesses, the effect of fever on PK and pharmacodynamics has received limited attention in the clinical literature. Although not conclusive, multiple investigations have examined the influence of fever on drug PK. This chapter aims to shed light on the often-ignored yet clinically important aspect of the effects of fever on drug PK by discussing multiple case studies and recent publications.

The assessment of the drug’s metabolism and its kinetics at both levels (in vitro and in vivo) is critical in pharmaceutical sciences. Enzyme kinetics is widely used in the evaluation and modeling of the disposition and the elimination of drugs. Easily performed drug metabolism (in vitro) investigations serve as a suitable screening mechanism to identify drug metabolites and explain their pathways for further examinations (in vivo). In this chapter, we have discussed different aspects related to metabolic kinetics (MK) such as uncatalyzed reaction, various order reactions involved in the metabolism of drug, MK of reactions involving enzyme catalysis (e.g., Michaelis–Menten equation), the role of the enzyme in the reaction kinetics, and different types of typical and atypical kinetics.

Results obtained from several investigations support gender-based guidelines issued by the Food and Drug Administration in 1993. These guidelines emphasize the inclusion of women in both bioavailability/bioequivalence (BE) investigations. Studies revealed intrasubject inconsistency in pharmacokinetic parameters for women over men; however, it is similar in most cases. This suggests that women can be excluded from few BE examinations based on sex-associated risk factors. Authors suppose that the obtained data may exhibit a substantial impression in designing and analyzing future investigations to examine sex-related responses.

The chapter discusses the principles of analytical method validation for identifying the pharmacokinetics, bioavailability (BA), and bioequivalence (BE) of both small and large molecules. The progress made in this field in the last two decades, including the most important agreements and problems concerning drug molecules, is also elaborated. The chapter discusses the validation of bioanalytical methods for the employment of BA and BE studies at both preclinical and clinical levels.

Measuring the drug and its metabolite in the biological sample provides a fundamental relationship between the dose administered and superior clinical efficacy. Hence, during analytical method development and validation, the drug concentration at the time of analysis and sample acquisition must be identical. The drugs and their metabolites might undergo degradation in acquired samples due to physical and chemical reactions, which results in the underestimation of the drug quantity in the original sample. Therefore understanding the factors influencing the stability of the drug and their metabolites, both in vitro and in vivo play a critical role in the bioanalysis and estimation of the drug pharmacokinetics. This chapter demonstrates different in vitro and in vivo factors that influence the drug and metabolite stability in the acquired biological sample with relevant examples.

Depicting a relationship between pharmacokinetics (PK) and pharmacodynamics (PD) is an imperative tool in the discovery and the development of the drug in the pharmaceutical field. Implementing PK/PD techniques in the initial stages of research may allow positive results in drug development. Further, efficient PK/PD investigations such as design, assessment, and interpretation of data will assist scientists in identifying a relationship amid PK and PD and help in understanding the mechanism of drug effect. Furthermore, it will also help determine various PK properties that are essential for designing an optimum compound. Moreover, PK/PD modeling may also enhance the potency of a molecule from in vitro to the in vivo setting, decrease the possible frequency of the in vivo animal investigations, and enhance translation of outcomes through preclinical to the clinical level. This chapter focuses on some crucial elements of effective PK/PD investigations such as how and why PK is essential, drug metabolism and toxicology, therapeutic drug response, the role of PK in the management of illness, the importance of silico tools to justify animal studies, patient counseling, and personalized therapy.

Pharmacokinetic (PK) and pharmacodynamics (PD) are of utmost importance in drug discovery and development. The safety and efficacy of the drugs and their products are highly dependent on their PK and PD properties. They are confirmed through various in silico studies and in vitro and in vivo investigations. Moreover, PK–PD modeling is widely employed to correlate the PK data with the PD data. As compared to other techniques, the microdialysis (MD) method is noninvasive, cheaper, and easy to operate. Its principle is based on the concentration gradient across the semipermeable membrane separated by two compartments. Herein, we have described in detail the use of MD to study PK–PD of drugs and its application in different models, especially in the PK–PD modeling. Further, we have discussed the preclinical and clinical use of MD in determining drug concentration for antimicrobial agents, central nervous systems drugs, autonomic nervous system drugs, and anticancer drugs.

Liposomes are one of the most successful drug delivery systems in the market. This stems from their general biocompatibility, tailorable physiochemical and biological characteristics, and capability to encapsulate hydrophilic and hydrophobic drugs. Various formulation and physiological factors alter the pharmacokinetics (PK) and pharmacodynamics of the liposomes. This chapter provides an insight into this important pharmaceutical carrier and offers a focused discussion on the various factors affecting the PK of the liposomal formulations. A viewpoint on the effect of various factors affecting the PK profile on the liposomal formulation is also presented.

For both patients (i.e., pediatric and geriatric) the products should be age appropriate, an essential criterion for achieving efficient drug therapy. Some frequently reported problems associated with these formulations may include the inappropriateness of the product with different age-groups, imperfect labeling, incompatibility, and unacceptability of drugs, which are the primary concern for causing errors in pediatric populations. During formulation, some factors such as formulation components (active pharmaceutical ingredient and excipients), substances used in primary packaging, and employed devices should be considered for their suitability and safety. However, for both populations, the oral route is widely preferred for delivering drugs for efficient results. Further, recent clinical investigations advocate the suitability of minitablets if we consider swallow-ability and acceptability of formulation as compared to other traditional liquid products. This chapter provides deep insight into different oral products for pediatric and geriatric patients. It discusses various alternative novel formulations (e.g., minitablets and flexible oral formulations) over conventional solid and liquid products.

Pregnancy is implicated with several alterations in maternal physiology as well as disease. However, it is supposed that during pregnancy the distribution of drugs as well as their effects are substantially varied. Physiological changes observed in pregnancy can considerably influence the pharmacokinetics (PK) and pharmacodynamics of the drug. A thorough understanding concerning physiology as well as gestation during pregnancy can help in an efficient therapy while reducing fetal as well as maternal risk. Several studies suggest that investigations on pregnant women are excluded due to both mother and fetal safety concerns. Moreover, approximately 66.6% of pregnant women have prescribed drugs, which are typically safe for either nonpregnant healthy women or healthy males. Furthermore, this chapter will provide in-depth insight into the PK of drugs in pregnant women and different factors affecting maternal–fetal drug transfer, the kinetics of maternal–fetal drug transfer, and a model to assess placental drug transport.

The exhaustive efforts commenced in the field of drug discovery. High-throughput screening in the drug discovery cycle leads to the generation of high-molecular-weight lipophilic molecules, which results in low bioavailability on account of poor pharmacokinetic (PK) profile. Recent reports say that about 40% of the newly discovered molecule belongs to the biopharmaceutical classification system (BCS) class II and BCS class IV. This chapter presents various techniques to improve the PK profile of existing drug molecules, especially those of hydrophobic nature, to enhance their solubility. Methods such as nanocrystals, cocrystals, amorphous solid dispersion, eutectic mixtures, freeze-drying, and salt formation have been discussed vide underlying literature citing the mechanisms involved in the improvement of PK by each method.

The advancement in technology has resulted in novel technology and product development by the biotech industry. Many of the drug manufacturers are shifting from conventional to biotech drugs. The development of these biotech products from small molecules requires considering different factors like pharmacokinetics (PK) parameters, stability, immunogenicity, and low cost. Thus one needs to deal with unique sets of challenges to achieve biotech products. Biotech products have a low PK profile because of their complex physiochemical properties, such as higher molecular weight and polarity. Poor PK is a key problem associated with biotech product development. Regulatory guidance described by International Conference on Harmonization (ICH) Q5 and ICH Q6B on biotechnological products are specific for biological and biotechnological products. The challenges concerning this process will be different compared to that of conventional drugs. Thus one needs to look at biotechnological products as a separate class to establish their PK properties. Biotechnological products can also be efficacious in treating some dreadful diseases (e.g., cancer, diabetes, and rheumatoid arthritis). Moreover, this chapter provides deep insight concerning the absorption, distribution, metabolism, and excretion of different biotech products, namely, RNA interference, protein, peptide, and monoclonal antibodies (MAbs). Additionally, PK modeling of MAbs includes noncompartmental, individual compartment, and population PK.

Increasing application on account of the rapid progress made by artificial intelligence (AI) in healthcare has brought upon a progressive paradigm shift. By combining relevant AI architectures with digitized data acquisition and sophisticated data validation techniques, AI-based technologies are expanding to unchartered areas. This chapter focuses on understanding recent novel innovations and practical clinical applications of AI in aiding the conventional healthcare industry. Breakthrough AI-based platforms that aid in critical sectors of the healthcare industry like disease diagnosis, robot-assisted surgery, patient rehabilitation, and use of smartphones/smart wearables for health monitoring and AI’s role in controlling and tackling COVID-19 like pandemics are summarized.