Drug Delivery Letters - Volume 15, Issue 3, 2025

Artificial intelligence (AI) is a branch of science and technology and an indispensable part of many fields of research in today’s world. Especially in the area of pharmaceutical research and drug development, AI has conferred numerous aids for many inventions as well as discoveries. There have been a lot of advancements and progress in the way that AI is incorporated into the pharmaceutical field, and with time, newer updates have come up which have eased many areas of this field.

This review aims to provide a basic understanding of and information related to the role of AI in the pharmaceutical field, be it research, drug development, or even the process of dispensing and compounding.

The literature study was carried out extensively through various databases like Google Scholar, PubMed, ScienceDirect, etc. to support this review. The information which was collected was analyzed and arranged accordingly.

From the survey that was carried out, it was found that there are many important roles of AI that have helped the pharmacists and researchers in multiple sectors of the pharmaceutical field. Thus, AI can be considered as a valuable tool to speed up different processes and results can be obtained fast.

The application of AI in the pharmaceutical sector has guided formulators and researchers in ways that were not possible earlier. Therefore, with the help of AI various manual and complex processes can now be easily accomplished without the unnecessary expenditure of resources, time, and money.

Low oral permeability and low aqueous solubility are considered significant obstacles in achieving systemic therapeutic concentration to show optimum pharmacological response. Pharmaceutical scientists endeavored to overcome the above-stated problem after utilizing various approaches like salt formation, pro-drugs, co-solvency, complexation, solubilization, pH adjustment, sold dispersion, hydrotrophy, and nanotechnology-based techniques.

Among these approaches, nanotechnology-based drug carrier systems have been investigated to address the challenges of the drugs exhibiting poor oral absorption. Essentially, these systems have the potential to overcome the limitations associated with the oral route of drug administration. Among various nano-technological tools, nanoemulsion plays an important role in the bioavailability enhancement of biopharmaceutical classification system Class II, and Class IV drugs, in general and, Class III, in particular.

A nanoemulsion is a colloidal system with a size in nanometers, an increased fraction of the dispersed phase, and intensified transparency. Either water is dispersed in oil (w/o type) or oil is dispersed in water (o/w type), and it has a longer shelf life.

Nanoemulsion is being utilized as an important drug carrier for bioavailability enhancement; however, it poses some challenges, such as clinical translation, large-scale manufacturing, and regulatory guidelines.

The current review aims to compile and discuss the problems faced in the delivery of drugs exhibiting poor oral absorption, challenges faced in oral drug delivery, oral absorption enhancement techniques, mechanism of oral uptake using nanoemulsion, various modifications of nanoemulsion, clinical status, large-scale manufacturing, regulatory status, and new prospects in the future.

Oral fast-melting tablets (FMTs) have been gaining popularity due to their advantages in resolving swallowing issues of conventional oral tablets. Cocoa butter is an excipient of choice to develop FMT with an acceptable taste and faster onset of action of the drug.

The present study aimed to prepare and characterize the amlodipine besylate-loaded cocoa butter FMTs.

Amlodipine besylate FMTs were prepared using a simple freezing (refrigeration) method. Cocoa butter (Form V) was used as the base to achieve a final tablet weight of 500 mg with drug and other functional excipients. The designed prototype tablet formulations were subjected to disintegration tests to determine the to determine the most robust batch. The formulation F4, containing 7% high-molecular-weight chitosan, exhibited the quickest disintegration time (DT) of 1.45 ± 0.10 min. Afterwards, the selected formulation, F4, was subjected to quality evaluation parameters.

Fourier transform infrared spectroscopy (FTIR) studies revealed that there was no incompatibility between amlodipine besylate, cocoa butter, and other excipients. The average hardness of the F4 formulation tablet batch was found to be 2.69 ± 0.21 kg/cm² and the friability was found to be 0.44%. The drug content in F4 tablets was found to be 102.38 ± 5.29% and showed an in-vitro drug release of 94.30 ± 2.63% within 30 min. Over a six-month stability testing period, the chosen F4 formulation did not significantly change in terms of tablet average weight, disintegration time, drug content, and in vitro dissolution rate at 25°C ± 2°C/ 60% ± 5% relative humidity.

Selected formulation F4 with 7% of high molecular weight chitosan exhibited good physical properties, indicating the suitability of cocoa butter as a base to produce FMTs with the aid of a natural super-disintegrant.

The oral bioavailability of Dabigatran (DGT) is significantly lower due to poor aqueous solubilization and p-gp efflux.

The prime objective was to enhance the solubilization of DGT using a self-nano-emulsifying drug delivery system (SNEDDS). DGT was administered with Piperine (PRN) to increase its availability for absorption by blocking p-gp. The secondary objective was to develop an accurate analytical method for DGT and PRN.

The first-order derivative spectrophotometry for simultaneous estimation of DGT and PRN was developed and validated. The solubility of the DGT and PRN was assessed in the chosen excipients of SNEDDS. The ternary phase diagram was constructed to assess the appropriate amount of oleic acid (OA), Capmul MCM C8 EP (CAP), and Transcutol P (TP). A risk assessment matrix and Ishikawa diagram were applied to scrutinize the critical parameters affecting the quality of SNEDDS. The optimization of SNEDDS was performed using a D-optimal mixture design. The amount of OA, CAP, and TP were carefully chosen as CMAs whereas globule size, poly-dispersibility index (PDI), emulsification time, and zeta potential were chosen as critical quality attributes (CQAs). The spring and parachute theory was applied to assess the effective amount of Soluplus to reduce precipitation. The designed SNEDDS was considered for the physicochemical parameters of SNEDDS. The optimized batch was converted into a solid SNEDDS (S-SNEDDS) by adsorbing it on the appropriate adsorbent and evaluating for flow property, X-ray Diffraction (XRD), and DGT-PRN release.

The developed method was robust, accurate, and precise for estimating DGT and PRN. The solubility study reveals that OA, CAP, and TP were screened as oil, surfactant, and co-surfactant. OA, CAP, and TP in a proportion of 1:2:1 were chosen from the ternary phase diagram. The optimal region was obtained from an overlay plot. The optimal SNEDDS was able to release DGT-PRN within two hours. The negative value of zeta potential (-11.5mv) assures the stability of SNEDDS. Soluplus (3%) was screened as a parachute which inhibited the precipitation. The optimum SNEDDS was converted into solid SNEDDS by adsorbing on Neusilin (NS). The alteration in results of FTIR, DSC, and XRD confirmed the change to amorphous form. The S-SNEDDS able to release the DGT-PRN within two hours.

The analytical method for estimating DGT and PRN was successfully developed and validated for its linearity, accuracy, and precision. SNEDDS containing DGT-PRN were developed with better performance. The D-optimal mixture design was adequate to optimize the SNEDDS. Soluplus was able to reduce the precipitation of the drugs. NS was explored to form S-SNEDDS and converted into a stable form. The amorphous S-SNEDDS has shown higher drug release. The optimized batch can be developed at an industrial scale.

Sepsis is a severe medical disorder that poses a significant risk to life, leading to elevated rates of sickness and mortality globally, reaching 11 million annually. It is distinguished by an imbalanced immune response to infection, which subsequently causes failure in several organs. Eugenol is obtained from clove oil and possesses various beneficial properties, such as antifungal, anti-inflammatory, antiviral, antioxidant, anticancer, and antibacterial effects.

The present study aimed to assess the effectiveness of eugenol-loaded chitosan nanoparticles (EC-NPs) in protecting against kidney damage caused by sepsis using the cecal ligation and puncture (CLP) model.

Thirty rats were divided into five groups: sham, sepsis, and septic rats treated with chitosan, eugenol, or EC-NPs.

Administration of EC-NPs dramatically enhanced renal function, as evidenced by the reduced urea, creatinine, and uric acid concentrations. Moreover, EC-NPs caused an elevation in glutathione reductase (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in addition to decreasing the production of malondialdehyde (MDA) and nitric oxide (NO). EC-NPs administration reduced the DNA damage in septic rats and partially restored the aberrant structure of renal tissues in septic rats. Furthermore, the immunohistochemical examination showed a marked decrease in tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) expression.

In conclusion, EC-NPs attenuated renal injury in septic rats through their anti-oxidant and anti-inflammatory activities and protection of DNA.

The development of novel drug carriers is invaluable to maximize therapeutic efficiency and improve specificity. Dioctadecyl-dimethylammonium bromide (DODAB): monoolein (MO) (1:2) liposomes exhibit non-lamellar phases in their core that improve the encapsulation ability of both hydrophobic and hydrophilic molecules. This study explores the use of this nanosystem for the therapeutic delivery of cytokines, specifically of leukemia inhibitory factor (LIF). Nanocarriers can overcome the drawbacks of direct cytokine administration, like poor bioavailability.

DODAB:MO (1:2) liposomes were produced by lipid film hydration, followed by extrusion, and used for encapsulating 0.125 and 0.25 µM LIF. The produced nanoparticles were characterized in terms of size and zeta potential, FTIR and STEM. LIF was quantified with an optimized Bradford method to determine encapsulation efficiencies, drug loading, and release profile. Cytotoxicity was assessed by hemolysis, and mouse myoblasts were used to validate bioactivity in vitro.

Neither the extrusion nor the protein incorporation steps promoted significant alterations in cytokine structure. LIF-containing liposomes DODAB (1:2) nanosystem were small (~200-300nm), positively charged (~50-60mV), non-toxic, and stable at physiological pH. Biophysical characterization identified liposomal formulation of 200 µM DODAB:MO (1:2) at 0.25 µM as the most efficient system. The bioactivity analysis showed an increase of ~20% in cell proliferation after 48h of incubation when compared to free mLIF. Also, the LIF-containing DODAB:MO (1:2) liposomal formulation, when exposed to serum, revealed a capacity to protect its cargo for up to 6 h.

The DODAB:MO (1:2) nanosystem was found to be efficient for cytokine delivery, stabilizing mLIF, and promoting its bioactivity with multiple applications.

Fenofibrate, a widely used lipid-lowering agent, exhibits limited bioavailability due to its BCS Class II status and poor aqueous solubility. Enhancing its solubility is crucial to improving therapeutic efficacy.

This study explored solubility enhancement via molecular docking-guided screening of transition metal complexes and inclusion complexes with beta-cyclodextrin (β-CD). Transition complexes of fenofibrate with copper acetate were synthesized at a 1:1 molar ratio in a methanol-water mixture (2:1). Additionally, inclusion complexes of these metal complexes with β-CD were prepared in a 1:1 molar ratio and dried. Physicochemical characterization was performed using FTIR, XRD, and SEM analyses. Molecular docking identified potential interactions and conformational stability of the complexes.

The aqueous solubility of fenofibrate increased significantly, 17-fold in the transition metal complex and 25-fold in the β-CD inclusion complex compared to the pure drug. The complexes demonstrated structural changes, including amorphization, which likely contributed to enhanced solubility. Molecular docking revealed strong interactions between fenofibrate, copper acetate, and β-CD, supporting the formation of stable complexes.

The results indicate that fenofibrate’s solubility can be markedly enhanced through complexation with transition metals and β-CD. These approaches, particularly the β-CD inclusion complexes, hold the potential for improving fenofibrate's bioavailability and therapeutic outcomes, offering a promising strategy for addressing solubility challenges in poorly water-soluble drugs.