Development Of Drug Formulations Research Articles

Synthesis and study of organo-modified silica based hydrogels: Rheological properties and drug release kinetics.

The method of synthesis of unmodified and organo-modified silica hydrogels and their composites with orotic acid as a model drug was developed. The hydrogels had a pH of 6.5-7.8. The particulate nature and highly porous structures of the hydrogel materials were revealed using scanning electron and optical microscopy methods. The content of aqueous phase in the hydrogels was 99% or more. In order to evaluate the possibility of their application as a basis for development of novel soft drug formulations and cosmetic compositions, rheological properties of the hydrogels and in vitro release kinetics of the drug were studied. The effects of synthesis conditions (increasing concentration of catalyst of silica sol formation, drug loading) and the silica matrix modification with various organic groups on the indicated properties were investigated. It was found that all synthesized hydrogels exhibited pseudoplasticity, thixotropy and controlled release of the drug, which are important for their potential application. However, in general, the indicated effects led to worsening the properties of the hydrogel materials in comparison with the unmodified silica hydrogels.

RAPID DISSOLUTION: DEVELOPMENT AND ASSESSMENT OF A NOVEL DRUG FORMULATION

This study focuses on the development and assessment of a novel fast-dissolving drug formulation aimed at improving drug delivery efficiency and patient compliance. The formulation was designed to dissolve rapidly in the oral cavity, facilitating quick absorption and onset of action. Through a systematic approach, the formulation's composition, including excipients and active pharmaceutical ingredients, was optimized to achieve rapid dissolution while maintaining stability and bioavailability. Various techniques, such as direct compression, freeze-drying, and spray drying, were explored to produce the fast-dissolving drug formulation. Evaluation of the formulation involved assessments of dissolution kinetics, drug release profile, physical characteristics, and pharmacokinetic parameters. The results demonstrate the potential of the fast-dissolving drug formulation to offer enhanced drug delivery and improved patient experience, making it a promising option for pharmaceutical development.

Nanotechnology for Pain Management.

Introduction: In the context of the current opioid crisis, non-pharmacologic approaches to pain management have been considered important alternatives to the use of opioids or analgesics. Advancements in nano and quantum technology have led to the development of several nanotransporters, including nanoparticles, micelles, quantum dots, liposomes, nanofibers, and nano-scaffolds. These modes of nanotransporters have led to the development of new drug formulations. In pain medicine, new liposome formulations led to the development of DepoFoam™ introduced by Pacira Pharmaceutical, Inc. (Parsippany, NJ, USA). This formulation is the base of DepoDur™, which comprises a combination of liposomes and extended-release morphine, and Exparel™, which comprises a combination of liposomes and extended-release bupivacaine. In 2021, Heron Therapeutics (San Diego, CA, USA) created Zynrelef™, a mixture of bupivacaine and meloxicam. Advancements in nanotechnology have led to the development of devices/patches containing millions of nanocapacitors. Data suggest that these nanotechnology-based devices/patches reduce acute and chronic pain. Methods: Google and PubMed searches were conducted to identify studies, case reports, and reviews of medical nanotechnology applications with a special focus on acute and chronic pain. This search was based on the use of keywords like nanotechnology, nano and quantum technology, nanoparticles, micelles, quantum dots, liposomes, nanofibers, nano-scaffolds, acute and chronic pain, and analgesics. This review focuses on the role of nanotechnology in acute and chronic pain. Results: (1) Nanotechnology-based transporters. DepoDur™, administered epidurally in 15, 20, or 25 mg single doses, has been demonstrated to produce significant analgesia lasting up to 48 h. Exparel™ is infiltrated at the surgical site at the recommended dose of 106 mg for bunionectomy, 266 mg for hemorrhoidectomy, 133 mg for shoulder surgery, and 266 mg for total knee arthroplasty (TKA). Exparel™ is also approved for peripheral nerve blocks, including interscalene, sciatic at the popliteal fossa, and adductor canal blocks. The injection of Exparel™ is usually preceded by an injection of plain bupivacaine to initiate analgesia before bupivacaine is released in enough quantity from the depofoarm to be pharmacodynamically effective. Finally, Zynrelef™ is applied at the surgical site during closure. It was initially approved for open inguinal hernia, abdominal surgery requiring a small-to-medium incision, foot surgery, and TKA. (2) Nanotechnology-based devices/patches. Two studies support the use of nanocapacitor-based devices/patches for the management of acute and chronic pain. A randomized study conducted on patients undergoing unilateral primary total knee (TKA) and total hip arthroplasty (THA) provided insight into the potential value of nanocapacitor-based technology for the control of postoperative acute pain. The results were based on 2 studies, one observational and one randomized. The observational study was conducted in 128 patients experiencing chronic pain for at least one year. This study suggested that compared to baseline, the application of a nanocapacitor-based Kailo™ pain relief patch on the pain site for 30 days led to a time-dependent decrease in pain and analgesic use and an increase in well-being. The randomized study compared the effects of standard of care treatment to those of the same standard of care approach plus the use of two nanocapacitor-based device/patches (NeuroCuple™ device) placed in the recovery room and kept in place for three days. The study demonstrated that the use of the two NeuroCuple™ devices was associated with a 41% reduction in pain at rest and a 52% decrease in the number of opioid refills requested by patients over the first 30 days after discharge from the hospital. Discussion: For the management of pain, the use of nano-based technology has led to the development of nano transporters, especially focus on the use of liposome and nanocapacitors. The use of liposome led to the development of DepoDur™, bupivacaine Exparel™ and a mixture of bupivacaine and meloxicam (Zynrelef™) and more recently lidocaine liposome formulation. In these cases, the technology is used to prolong the duration of action of drugs included in the preparation. Another indication of nanotechnology is the development of nanocapacitor device or patches. Although, data obtained with the use of nanocapacitors are still limited, evidence suggests that the use of nanocapacitors devices/patches may be interesting for the treatment of both acute and chronic pain, since the studies conducted with the NeuroCuple™ device and the based Kailo™ pain relief patch were not placebo-controlled, it is clear that additional placebo studies are required to confirm these preliminary results. Therefore, the development of a placebo devices/patches is necessary. Conclusions: Increasing evidence supports the concept that nanotechnology may represent a valuable tool as a drug transporter including liposomes and as a nanocapacitor-based device/patch to reduce or even eliminate the use of opioids in surgical patients. However, more studies are required to confirm this concept, especially with the use of nanotechnology incorporated in devices/patches.

A Patent Review on Cardiotoxicity of Anticancerous Drugs.

Chemotherapy-induced cardiotoxicity is an increasing concern and it is critical to avoid heart dysfunction induced by medications used in various cancers. Dysregulated cardiomyocyte homeostasis is a critical phenomenon of drug-induced cardiotoxicity, which hinders the cardiac tissue's natural physiological function. Drug-induced cardiotoxicity is responsible for various heart disorders such as myocardial infarction, myocardial hypertrophy, and arrhythmia, among others. Chronic cardiac stress due to drug toxicity restricts the usage of cancer medications. Anticancer medications can cause a variety of adverse effects, especially cardiovascular toxicity. This review is focused on anticancerous drugs anthracyclines, trastuzumab, nonsteroidal anti-inflammatory medications (NSAIDs), and immune checkpoint inhibitors (ICI) and associated pathways attributed to the drug-induced cardiotoxicity. Several factors responsible for enhanced cardiotoxicity are age, gender specificity, diseased conditions, and therapy are also discussed. The review also highlighted the patents assigned for different methodologies involved in the assessment and reducing cardiotoxicity. Recent advancements where the usage of trastuzumab and bevacizumab have caused cardiac dysfunction and their effects alone or in combination on cardiac cells are explained. Extensive research on patents associated with protection against cardiotoxicity has shown that chemicals like bis(dioxopiperazine)s and manganese compounds were cardioprotective when combined with other selected anticancerous drugs. Numerous patents are associated with drug-induced toxicity, prevention, and diagnosis, that may aid in understanding the current issues and developing novel therapies with safer cardiovascular outcomes. Also, the advancements in technology and research going on are yet to be explored to overcome the present issue of cardiotoxicity with the development of new drug formulations.

Precise Therapy Using the Selective Endogenous Encapsidation for Cellular Delivery Vector System.

Interindividual variability in drug response is a major problem in the prescription of pharmacological treatments. The therapeutic effect of drugs can be influenced by human genes. Pharmacogenomic guidelines for individualization of treatment have been validated and used for conventional dosage forms. However, drugs can often target non-specific areas and produce both desired and undesired pharmacological effects. The use of nanoparticles, liposomes, or other available forms for drug formulation could help to overcome the latter problem. Virus-like particles based on retroviruses could be a potential envelope for safe and efficient drug formulations. Human endogenous retroviruses would make it possible to overcome the host immune response and deliver drugs to the desired target. PEG10 is a promising candidate that can bind to mRNA because it is secreted like an enveloped virus-like extracellular vesicle. PEG10 is a retrotransposon-derived gene that has been domesticated. Therefore, formulations with PEG10 may have a lower immunogenicity. The use of existing knowledge can lead to the development of suitable drug formulations for the precise treatment of individual diseases.

Statistical Applications in Pharmaceutical Product Development: A Comprehensive Review

The pharmaceutical industry often depends on statistics to improve product quality, optimize the compositions, streamline operations, and conform to regulatory requirements. In Bio Equivalency investigations, Statistics plays an integral role in decision-making while demonstrating the similarity between the test and reference products. In this review, we explore how statistics play a crucial role in pharmaceutical product development. We start with examining experiments, where statistics help scientists find the best combinations of ingredients and manufacturing conditions. We explored different types of experiments, like factorial designs, Plackett-Burman designs, Box-Behnken designs, and Taguchi designs. While optimizing the formulations and process parameters, these methodologies assist researchers in making meaningful conclusions supported by statistical inference. The next sections include Response Surface Methodology (RSM) and Mixture Designs, which help in the development of drug formulations and the comprehension of complex responses. The development of pharmaceuticals is made simpler by these approaches. Then, we examine optimal designs like A-optimal, I-optimal, and D-optimal. A-optimal designs save resources, I-optimal designs focus on precise estimates, and D-optimal designs are great for screening and getting accurate results. These designs help scientists make decisions based on data. The starting point for demonstrating dissolution similarity between generic and reference products is the statistical approach. This paper examines the use of model-dependent techniques, such as zero-order, first-order, Higuchi, and Weibull models, and model-independent techniques such as F1, F2, Bootstrap, MSD, and PCA techniques, it analyzes important parameters and bounds that are essential for determining the dissolution similarity. In the field of biostatistics, we discuss how statistics ensures that generic drugs are safe and work just as efficiently as brand-name drugs. Both regulatory approval and patient safety rely on this. We briefly discuss statistical process control (SPC) in closing. SPC checks that drugs/drug products are consistently of quality using graphs and figures. It facilitates the production of consistently effective pharmaceuticals by organizations. Advanced statistical techniques, including data mining, machine learning, and artificial intelligence, are revolutionizing the pharmaceutical industry. These tools enhance drug discovery, optimize manufacturing processes, and pave the way for personalized medicine. As real-time monitoring and predictive analytics become integral, the future holds exciting possibilities for improving patient outcomes. This review shows how statistics are like a guiding tool in the pharmaceutical industry. Whether it's in the lab or in manufacturing, statistics play a big role in making sure patients get the best medicines possible.

Ethanol-based solubility-enabling oral drug formulation development: Accounting for the solubility-permeability interplay

The aim of the current work was to investigate the key factors that govern the success/failure of an ethanol-based solubility-enabling oral drug formulation, including the effects of the ethanol on the solubility of the drug, the permeability across the intestinal membrane, the drug's dissolution in the aqueous milieu of the gastrointestinal tract (GIT), and the resulting solubility-permeability interplay. The concentration-dependent effects of ethanol-based vehicles on the solubility, the in-vitro Caco-2 permeability, the in-vivo rat permeability, and the biorelevant dissolution of the BCS class II antiepileptic drug carbamazepine were studied, and a predictive model describing the solubility-permeability relationship was developed. Significant concentration-dependent solubility increase of CBZ was obtained with increasing ethanol levels, that was accompanied by permeability decrease, both in Caco-2 and in rat perfusion studies, demonstrating a tradeoff between the increased solubility afforded by the ethanol and a concomitant permeability decrease. When ethanol absorption was accounted for, an excellent agreement was achieved between the predicted permeability and the experimental data. Biorelevant dissolution studies revealed that minimal ethanol levels of 30 % and 50 % were needed to fully dissolve 1 and 5 mg CBZ dose respectively, with no drug precipitation.In conclusion, key factors to be accounted for when developing ethanol-based formulation include the drug's solubility, permeability, the solubility-permeability interplay, and the drug dose intended to be delivered. Only the minimal amount of ethanol sufficient to solubilize the drug dose throughout the GIT should be used, and not more than that, to avoid unnecessarily permeability loss, and to maximize overall drug absorption.

Activity of the Di-Substituted Urea-Derived Compound I-17 in Leishmania In Vitro Infections.

Protein synthesis has been a very rich target for developing drugs to control prokaryotic and eukaryotic pathogens. Despite the development of new drug formulations, treating human cutaneous and visceral Leishmaniasis still needs significant improvements due to the considerable side effects and low adherence associated with the current treatment regimen. In this work, we show that the di-substituted urea-derived compounds I-17 and 3m are effective in inhibiting the promastigote growth of different Leishmania species and reducing the macrophage intracellular load of amastigotes of the Leishmania (L.) amazonensis and L. major species, in addition to exhibiting low macrophage cytotoxicity. We also show a potential immunomodulatory effect of I-17 and 3m in infected macrophages, which exhibited increased expression of inducible Nitric Oxide Synthase (NOS2) and production of Nitric Oxide (NO). Our data indicate that I-17, 3m, and their analogs may be helpful in developing new drugs for treating leishmaniasis.

Systematic Review On Major Antiviral Phytocompounds from Common Medicinal Plants Against SARS-CoV-2.

Developing potential and effective vaccine is also time consuming and challenging. The huge resource of plants around us has rich source of potent antiviral compounds. Some of these molecules may serve as tremendously potent lead molecules whose slight structural modifications may give us highly bioactive antiviral derivatives of phytocompounds. Every geographical region is rich in unique plant biodiversity and hence every corner of the world with rich plant biodiversity can serve as abode for potential magical phytocompounds most of which have not been extensively explored for development of antiviral drug formulations against various viruses like HIV, HPV etc., and the Coronavirus, also known as SARS-CoV-2 which causes the disease COVID-19. Several phytocompounds from various medicinal plants have already been screened using in silico tools and some of them have yielded promising results establishing themselves as potent lead molecules for development of drugs against the highly mutating SARS-CoV-2 virus and thus these phytocompounds may be beneficial in treating COVID-19 and help human to win the life threatening battle against the deadly virus. The best advantage is that these phytocompounds being derived from nature in most of the cases, come with minimum or no side effects compared to that of chemically synthesized conventional bioactive compounds and are indigenously available hence are the source of cost effective drug formulations with strong therapeutic potentials.

Current Challenges and Approaches on Delivery of Protein Based Formulations

Numerous obstacle crops up in the path of developing efficient protein-based formulations and administration in humans for their therapeutic effect. The challenges starts from protein synthesis to it’s handling procedure, stability, storage, excipients compatibility, scale up, analysis, validation, tissue targeting, in-vivo bioavailability, immunogenic reactions, etc., In the field of protein drug development, various novel methods and techniques have been evolved and continuing the research to face those challenges to bring out potential drug formulations and its delivery system to the market. It is vital to develop various strategies for protecting the integrity of proteins, increasing their availability in the body, decreasing immunological responses, transporting and target to particular tissues or cells. This current review focuses on to understand the problems, challenges encountering and the best approaches for protein based drug formulation development. It is one of roadmap to plan various research activities for continual improvement of therapeutic applications of newly developing protein drugs in this area.

A Rapid 3-Day Excipient Screening Methodology and its Application in Identifying Chemical Stabilizers for Solid Formulations with Mixed Mechanisms of Degradation.

This study outlines a practical approach for assessing chemical instability by heating the drug-excipient binary mixtures or multi-excipient formulations at 75°C for 3days before characterization. Differentiating itself from other excipient compatibility methods, our methodology necessitates a saturated aqueous slurry rather than arbitrarily fixed water content. This allows bulk and surface water in the excipient to contribute to drug degradation. The synergistic impact of surface water and elevated temperature expedites degradation kinetics, resulting in accelerated data generation. Among excipient compatibility methods available, our method is quantitative and merges with traditionally used methodologies. The devised nomograph enables extrapolation of shelf life at 20°C from experimental data obtained at 75°C. This methodology also helped identify stabilizers for the drug NVS-1 where traditional excipient compatibility programs had failed. Incorporation of monovalent salts, such as sodium/potassium chloride and sodium bicarbonate at 5% w/w, significantly enhanced the chemical stability of NVS-1, ensuring stable tablet formulations. Our hypothesis posits that stabilization is due to increased ionic strength in the slurry, which stabilizes an induced dipole within the polar NVS-1 drug. Additionally, the presence of ions in the moisture layer is anticipated to stabilize π-π stacking of two planar aromatic NVS-1 molecules. The expedited generation of experimental data allowed the identification of inorganic salts to supplement a standard excipient compatibility screening panel. Considering the economic implications of stability testing methodologies in effort, cost, and duration, a faster turnaround in chemical stability data enhances formulation selection. This ultimately facilitates the development of drug formulations with greater efficiency without delays.

Physicochemical and pharmacotechnical characterization of Prussian blue for future Prussian blue oral dosage forms formulation

Ferric hexacyanoferrate, Fe4 [Fe(CN)6]3 · xH2O, known as Prussian blue (PB), has proven its effectiveness as an antidote in cases of accidental poisoning or poisoning caused by radioactive materials such as cesium (Cs) and thallium (Tl); which due to their solubility in water, when absorbed by the human body, cause serious damage to vital organs. The local development of a drug with PB as an active ingredient arises as a response to the civil and military needs established within the Ministry's pharmacy request for national defense. This fact contemplates the circumstances related to public health protection in the nuclear, radiological, biological and chemical (NRBQ) of the emergency institutions in health and national security. In this paper and by using various analytical techniques, the characterization of the locally synthesized PB with pharmaceutical quality has been described, as a first step to predict its behavior in the preparation of a drug that contains it as an active ingredient.The research findings demonstrate that locally synthesized PB is suitable for use in oral dosage forms, enabling the local development of drug formulations incorporating PB, thus being able to potentially become a main resource in the treatment of Cs and Tl poisoning in any accidental or intended of the population. This development opens up the possibility of creating drug formulations that incorporate PB at a local level, making it a potentially significant resource in the treatment of Cs and Tl poisoning. The ability to locally produce and utilize PB in oral dosage forms could be crucial in addressing cases of accidental or intentional exposure within the population. This advancement not only contributes to the scientific understanding of PB but also holds promising implications for practical applications in public health and emergency situations.

Preparation, characterization, in-vitro and toxicological evaluation of carbopol based nanogels for solubility enhancement of Valsartan

Solubility is an essential criterion for attaining desired concentration of the drug within the systemic circulation to ensure intended pharmacological action. The main setback for the formulation development of new chemical entities and generic drugs is their lower aqueous solubility. Therefore, a drug carrier system is needed which not only enhances the solubility of low aqueous soluble drugs but also maintains a constant pharmacological action of drugs within predetermined intervals of time. For this purpose, authors prepared carbopol 934-co-poly(itaconic acid) (CPcPIA) nanogels by the free radical polymerization technique for the solubility enhancement of Valsartan. The polymeric nanogels were characterized and studied for further evaluation. FTIR studies indicated no interactions between the drug and nanogel contents. SEM showed a porous and sponged structure of particles without any agglomeration. Similarly, higher thermal stability was detected for the fabricated nanogel compared to its constituents, while reduction in crystallinity of the drug and excipients was shown by XRD analysis, indicating the amorphous nature of the polymeric nanogels. Average particle size and zeta potential of prepared nanogels were found 290.32 nm and –8.32 mV, respectively. Furthermore, various studies such as sol-gel fraction, dynamic swelling, drug loading, in-vitro drug release studies, solubility, and toxicity study were conducted for the developed nanogels. A significant increase in the solubility of Valsartan (2.002, 2.976, and 3.543 mg/mL) was observed by polymeric nanogels in pH 1.2, deionized distilled water, and pH 7.4 as compared to reference product. Toxicity study indicated no toxic effect of prepared nanogels on rabbit's species. Thus, it can be demonstrated from the results that synthesized nanogels are not only limited to a specific class of drug but the solubility of all low aqueous soluble drugs can be enhanced by the prepared networks of nanogels.

Anticancer Property of Digera muricata Leaf Extract: An In Vitro Study.

Aim The aim was to evaluate the anticancer potential of Digera muricata ethanolicleaf extract on MG-63 osteosarcoma cell lines. Materials and methods The anti-cancer properties of Digera muricata ethanolic leaf extract were evaluated on osteosarcoma cell lines using 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the morphological changes in MG-63 cells were assessed after 24 hours using microscopic observation. Additionally, fluorescence microscopy was employed to evaluate the apoptotic changes after acridine orange/ethidium bromide (AO/EtBr) dual staining. Results The MTT assay revealed a dose-dependent cell death. The cell viability decreased with increase in concentrations of the extract, The cell viability was 89.98 ± 4.89 percentage at 25 μg/ml and 15.64 ± 3.64 percentage at 200 μg/ml concentrations. A concentartion of 116.95 μg/ml showed 50% inhibition (IC50). The morphological and dual staining studies also showed the extract's effectiveness in inducing apoptosis. Conclusion The ethanolic leaf extract of D. muricatacould impart good antiproliferative activity in MG-63 cell lines. The extract could also induce apoptosis and hence, it may be considered as a potential anticancer agent for the development of drug formulation for the treatment of osteosarcoma.

Lenvatinib-Loaded Poly(lactic-co-glycolic acid) Nanoparticles with Epidermal Growth Factor Receptor Antibody Conjugation as a Preclinical Approach to Therapeutically Improve Thyroid Cancer with Aggressive Behavior.

Lenvatinib, a tyrosine kinase inhibitor (TKI) approved for the treatment of progressive and radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), is associated with significant adverse effects that can be partially mitigated through the development of novel drug formulations. The utilization of nanoparticles presents a viable option, as it allows for targeted drug delivery, reducing certain side effects and enhancing the overall quality of life for patients. This study aimed to produce and assess, both in vitro and in vivo, the cytotoxicity, biodistribution, and therapeutic efficacy of lenvatinib-loaded PLGA nanoparticles (NPs), both with and without decoration using antibody conjugation (cetuximab), as a novel therapeutic approach for managing aggressive thyroid tumors. Poly(lactic-co-glycolic acid) nanoparticles (NPs), decorated with or without anti-EGFR, were employed as a lenvatinib delivery system. These NPs were characterized for size distribution, surface morphology, surface charge, and drug encapsulation efficiency. Cytotoxicity was evaluated through MTT assays using two cellular models, one representing normal thyroid cells (Nthy-ori 3-1) and the other representing anaplastic thyroid cells (CAL-62). Additionally, an in vivo xenograft mouse model was established to investigate biodistribution and therapeutic efficacy following intragastric administration. The NPs demonstrated success in terms of particle size, polydispersity index (PDI), zeta potential, morphology, encapsulation efficiency, and cetuximab distribution across the surface. In vitro analysis revealed cytotoxicity in both cellular models with both formulations, but only the decorated NPs achieved an ID50 value in CAL-62 cells. Biodistribution analysis following intragastric administration in xenografted thyroid mice demonstrated good stability in terms of intestinal barrier function and tumor accumulation. Both formulations were generally well tolerated without inducing pathological effects in the examined organs. Importantly, both formulations increased tumor necrosis; however, decorated NPs exhibited enhanced parameters related to apoptotic/karyolytic forms, mitotic index, and vascularization compared with NPs without decoration. These proof-of-concept findings suggest a promising strategy for administering TKIs in a more targeted and effective manner.

Contribution of the Dynamic Intestinal Absorption Model (Diamod) to the Development of a Patient-Centric Drug Formulation.

Compound X is a weak basic drug targeting the early stages of Parkinson's disease, for which a theoretical risk assessment has indicated that elevated gastric pH conditions could potentially result in reduced plasma concentrations. Different in vitro dissolution methodologies varying in level of complexity and a physiologically based pharmacokinetic (PBPK) absorption model demonstrated that the dissolution, solubility, and intestinal absorption of compound X was indeed reduced under elevated gastric pH conditions. These observations were confirmed in a crossover pharmacokinetic study in Beagle dogs. As a result, the development of a formulation resulting in robust performance that is not sensitive to the exposed gastric pH levels is of crucial importance. The dynamic intestinal absorption MODel (Diamod), an advanced in vitro gastrointestinal transfer tool that allows to study the gastrointestinal dissolution and interconnected permeation of drugs, was selected as an in vitro tool for the formulation optimization activities given its promising predictive capacity and its capability to generate insights into the mechanisms driving formulation performance. Different pH-modifiers were screened for their potential to mitigate the pH-effect by decreasing the microenvironmental pH at the dissolution surface. Finally, an optimized formulation containing a clinically relevant dose of the drug and a functional amount of the selected pH-modifier was evaluated for its performance in the Diamod. This monolayer tablet formulation resulted in rapid gastric dissolution and supersaturation, inducing adequate intestinal supersaturation and permeation of compound X, irrespective of the gastric acidity level in the stomach. In conclusion, this study describes the holistic biopharmaceutics approach driving the development of a patient-centric formulation of compound X.

Improve Bioequivalence predictions with PAMPA Dissolution using Etoricoxib and five other Drug Formulations

In the generic drug formulation development, pilot bioequivalence (BE) study with a small group of subjects is the current practice for oral formulation prediction. However, due to the difficulty in differentiating the variation between subject and drug formulation with the current BE practice，a new instrument called PAMPA Dissolution is proposed to eliminate the subjects variation and to enhance the correlation between in vitro to in vivo absorption in BE study. PAMPA Dissolution simultaneously measures drug dissolution (Cb) and permeation (Pe), following the validated oral drug absorption equation F (drug absorbed) = Cb*Pe*Area. The use of biorelevant media further allows this device to mimic in vivo conditions closely. Formulations of 60 mg etoricoxib tablets were studied to verify system reproducibility and BE prediction to demonstrate the potential of PAMPA Dissolution in generic drug development. The BE predictions between generic and brand etoricoxib tablets (test/reference) from this system produced a Cmax value of 99.0% and AUC value of 99.1%, indicating that PAMPA Dissolution predictions conform with bioequivalence results. Other oral formulations of valsartan/hydrochlorothiazide, ezetimibe, telmisartan, and amlodipine were also tested for their permeation (Pe) by PAMPA Dissolution. Results of drug permeation compared to the literature values indicates that the PAMPA Dissolution is reliable and precise in formulation development.

Lipid-Based Nano-Formulation Development to Enhance Oral Bioavailability of Weakly Aqueous-Soluble Drug for Obesity and Hypertension

The most practical method of drug delivery is oral administration because it has a high rate of patient compliance. However, there are significant obstacles to effective oral medication delivery, including low drug enzymatic/metabolic stability and poor water solubility. Especially in the development of drug formulations for the treatment of obesity and hypertension. This research article aims to formulate solid lipid nanoparticles (SLN) of Fucoxanthin and Ramipril by the emulsification and ultrasonication methods. The nanoparticles size, polydispersity index, and the zeta potential, among other parameters, were computed. In addition, FT-IR analysis of compatibility tests between the SLNs and the loaded drug and in vitro drug release experiments were carried out. Lipid-based nano preparations have drawn plenty of interest as efficient vehicles to increase the oral bioavailability of these kinds of medications. We observed that lipid nanoparticles, have enhanced the oral bioavailability of poorly water-soluble drugs used for obesity and hypertension. Provided the above information, formulated SLNs should be further investigated using cutting-edge scientific methodologies to improve its bioavailability.

Supramolecular Nucleic Acid-Based Organosilica Nanoparticles Responsive to Physical and Biological Inputs.

Organosilica nanoparticles that contain responsive organic building blocks as constitutive components of the silica network offer promising opportunities for the development of innovative drug formulations, biomolecule delivery, and diagnostic tools. However, the synthetic challenges required to introduce dynamic and multifunctional building blocks have hindered the realization of biomimicking nanoparticles. In this study, capitalizing on our previous research on responsive nucleic acid-based organosilica nanoparticles, we combine the supramolecular programmability of nucleic acid (NA) interactions with sol-gel chemistry. This approach allows us to create dynamic supramolecular bridging units of nucleic acids in a silica-based scaffold. Two peptide nucleic acid-based monoalkoxysilane derivatives, which self-assemble into a supramolecular bis-alkoxysilane through direct base pairing, were chosen as the noncovalent units inserted into the silica network. In addition, a bridging functional NA aptamer leads to the specific recognition of ATP molecules. In a one-step bottom-up approach, the resulting supramolecular building blocks can be used to prepare responsive organosilica nanoparticles. The supramolecular Watson-Crick-Franklin interactions of the organosilica nanoparticles result in a programmable response to external physical (i.e., temperature) and biological (i.e., DNA and ATP) inputs and thus pave the way for the rational design of multifunctional silica materials with application from drug delivery to theranostics.

Pediatric Drug Development: Reviewing Challenges and Opportunities by Tracking Innovative Therapies.

The paradigm of pediatric drug development has been evolving in a "carrot-and-stick"-based tactic to address population-specific issues. However, the off-label prescription of adult medicines to pediatric patients remains a feature of clinical practice, which may compromise the age-appropriate evaluation of treatments. Therefore, the United States and the European Pediatric Formulation Initiative have recommended applying nanotechnology-based delivery systems to tackle some of these challenges, particularly applying inorganic, polymeric, and lipid-based nanoparticles. Connected with these, advanced therapy medicinal products (ATMPs) have also been highlighted, with optimistic perspectives for the pediatric population. Despite the results achieved using these innovative therapies, a workforce that congregates pediatric patients and/or caregivers, healthcare stakeholders, drug developers, and physicians continues to be of utmost relevance to promote standardized guidelines for pediatric drug development, enabling a fast lab-to-clinical translation. Therefore, taking into consideration the significance of this topic, this work aims to compile the current landscape of pediatric drug development by (1) outlining the historic regulatory panorama, (2) summarizing the challenges in the development of pediatric drug formulation, and (3) delineating the advantages/disadvantages of using innovative approaches, such as nanomedicines and ATMPs in pediatrics. Moreover, some attention will be given to the role of pharmaceutical technologists and developers in conceiving pediatric medicines.