Journal of Pharmaceutical and BioTech Industry

Current estimates suggest that Africa contains about 14% of the world’s population and accounts for 20% of the global burden of disease. Yet, it accounts for a mere 3% of clinical trials globally. The time is ripe—even overdue—for determining how best to direct future health research efforts. In response, a call has been heard for a continent-wide Africa-centric research ethics framework to redirect health research in Africa, as well as address the health research ethics malpractices that have violated the rights, dignity and well-being of participating African communities. Nevertheless, we should remain aware of what already exists and what continues to be of value. Creating parallel frameworks risks fragmentation of research, increased costs in having to meet differing requirements and delayed access of patients to new treatments. Existing international consensus documents which have evolved and been fine-tuned over time, offer guidance for ensuring ethical instigation and management of health research. The Declaration of Helsinki enunciates clear principles for ensuring the ethical conduct of clinical research, while CIOMS’ 2016 International Ethical Guidelines for Health-related Research involving Humans offer guidance for implementing these principles. It is failure to apply existing ethical principles and guidance—and not any perceived inadequacy of those principles—that has resulted in sub-optimal protection of African research participants. Full article

Background: Off-label nebulization of tranexamic acid (TXA) solution is common practice for the treatment of hemoptysis. However, data regarding nebulization protocols, resulting aerodynamic parameters of the generated aerosol, and corresponding biopharmaceutical parameters are missing. The aim of this in vitro study was to investigate the aerosol characteristics of nebulized sterile, aqueous TXA solution. Methods: TXA solution 100 mg/mL was nebulized for 2 min by a multi-dose vibrating mesh nebulizer using 15 L/min and 30 L/min air flow rates. The generated aerosol was analyzed by a Next Generation Cascade Impactor. For each air flow rate, the mean Fine Particle Dose (FPD), Fine Particle Fraction (FPF), the Mass Median Aerodynamic Diameter (MMAD), and Geometric Standard Deviation (GSD) were quantified. Results: Nebulization at 15 L/min air flow rate resulted in a MMAD of 6.68 ± 0.23 µm and GSD of 2.02 ± 0.16. The FPD < 5 µm was 16.56 ± 0.45 mg, the FPF < 5 µm 28.91 ± 3.40%. Nebulization at 30 L/min air flow rate revealed a MMAD of 5.18 ± 0.12 µm and GSD of 2.14 ± 0.10. The FPD < 5 µm was 16.30 ± 1.38 mg, the FPF < 5 µm 35.43 ± 0.59%. Conclusions: Nebulization of TXA 100 mg/mL solution by a specified vibrating mesh nebulizer generated an aerosol particle distribution and deposition pattern suitable for the treatment of hemoptysis with bronchial origin. Full article

Developing a new drug costs approximately one to three billion dollars and takes around ten years; however, this process has only a ten percent success rate. To address this issue, new technologies that combine artificial intelligence (AI) and quantum computing can be leveraged in the pharmaceutical industry. The RSA cryptographic algorithm, developed by Rivest, Shamir, and Adleman in 1977, is one of the most widely used public-key encryption schemes in modern digital security. Its security foundation lies in the computational difficulty of factoring the product of two large prime numbers, a problem considered intractable for classical computers when the key size is sufficiently large (e.g., 2048 bits or more). A future application of using a detailed structural model of a protein is that digital drug design can be used to predict potential drug candidates, thereby reducing or eliminating the need for time-consuming laboratory and animal testing. Knowing the molecular structure of a possible candidate drug can provide insights into how drugs interact with targets at an atomic level, at significantly lower expenditures, and with maximum effectiveness. AI and quantum computers can rapidly screen out potential new drug candidates, determine the toxicity level of a known drug, and eliminate drugs with high toxicity at the beginning of the drug development phase, thereby avoiding expensive laboratory and animal testing. The Food and Drug Administration (FDA) and other regulatory bodies are increasingly supporting the use of in silico to in vitro/in vivo validation methods and assessments of drug safety and efficacy. Full article

The development of novel dosage forms of vitamin B₁₂ is an urgent task for addressing vitamin deficiency in individuals with gastrointestinal diseases or those following stringent dietary limitations. The study illustrates the fundamental possibility of employing a non-toxic and biocompatible organosilicon hydrogel with significant sorption capacity for B₁₂ delivery. Research indicated that 40 min of incubation suffices for optimal loading efficiency, influenced by both external diffusion and intradiffusion factors. The release of B₁₂ in a medium that mimics the human gastrointestinal tract transpires almost entirely within a timeframe that aligns with physiological conditions. Consequently, organosilicon hydrogels serve as potential vehicles for the administration of vitamin B₁₂. Full article

Tablet surface defects are typically controlled by visual inspection in the pharmaceutical industry. This is an insufficient response variable for knowledge-based formulation and process development, and it results in rather limited robustness of the control strategy. In this article, we present an analytical method for the quantitative characterization of visual tablet surface defects. The method involves analysis of the tablet surface by a digital microscope to obtain optical images and three-dimensional surface scans. Pre-processing procedures are applied for the simplification of the data to allow the detection of the imprint characters and tablet surface structures by a Faster R-CNN object detection model. Geometrical variables like perimeter and area were derived from the results of the object detection model and statistically analyzed for a selected number of tablets. The analysis allowed the development of product-specific acceptance criteria by a small reference dataset, and the quantitative evaluation of sticking, picking, chipping, and abrasion defects. The method showed high precision and sensitivity and demonstrated robust detection of visual tablet surface defects without false negative results. The image analysis was automated, and the developed algorithm can be operated by a simple routine on a standard computer in a few minutes. The method is suitable for industrial use and enables advancements in industrial formulation and process development while providing a novel opportunity for the quality control of visual tablet surface defects. Full article

Poor drug entrapment, burst release, and variable drug release profiles are the most critical challenges associated with biodegradable-polymer-based microspheres. In this study, biodegradable-polymer-based microspheres were used to entrap an antiplatelet drug, eptifibatide, using a single-emulsion solvent evaporation method. Critical challenges associated with biodegradable-polymer-based microspheres were addressed by incorporating different additives in the drug or polymer phase. Additives such as hydroxy propyl beta cyclodextrins (HPβCD), carboxy methyl cellulose sodium (Na CMC), and trehalose were added to the drug phase to evaluate their impact on the entrapment and stability of eptifibatide. The effect of the addition of additives such as polyvinyl alcohol (PVA), polyethylene glycol-400 (PEG-400), and methoxy polyethylene glycol phospholipid dimyristoyl phosphatidylethanolamine (mPEG-2000-DMPE, Na) to the polymer phase on the release profile of eptifibatide was evaluated. The inclusion of HPβCD resulted in good drug entrapment and helped control the initial unwanted burst release. Including Na CMC increased eptifibatide entrapment from 75% to 95%. Trehalose helped prevent the degradation of eptifibatide during lyophilization, and including PVA and PEG-400 reduced the lag phase and led to a controlled-release profile. Thus, including additives in the formulation can effectively improve the drug load and address issues associated with biodegradable-polymer-based microspheres. Full article

Aims: To describe and analyze trends in the utilization, spending, and average per prescription price of disease-modifying antirheumatic drugs (DMARDs) in the US Medicaid population. Methods: Using the publicly available national outpatient Medicaid State Drug Utilization Data, a retrospective, descriptive trend analysis was conducted on DMARDs from 1991 to 2022. Annual prescription counts and reimbursement amounts were calculated for nonbiologic and biologic DMARDs. Average per prescription price and Market share competition were calculated and analyzed for DMARDs. Results: Medicaid utilization of nonbiologic peaked in 2021 with 884,000 while biologic DMARDs with 688,000 prescriptions. In 2022, biologic utilization took the lead and exceed nonbiologic with 1.5 million prescriptions. Over the last 32 years, biologics captured 94% of Medicaid expenditures toward DMARDs, of which, 56% was toward adalimumab alone. On the other hand, spending on conventional DMARDs accounted for 33% while 67% accounted toward Janus Kinase Inhibitors. Biologic DMARDs average prices increased from around $800 to around $6000. However, the average adalimumab price increased 12-fold from around $1200 in 2003 to over $15,000 in 2021. Medicaid spending toward adalimumab increased by 179%. Conclusions: The substantial increase of DMARDs utilization and expenditure contributed significant burden to Medicaid budget. Introducing biosimilars into the market in the past few years is eroding the market share for several established biologics. Further cost-containment policies may be necessary for costly DMARD pharmacotherapy. Full article

This study investigates the comparative impact of fermentation versus conventional extraction methods on the bioactive potency of “FERMENZA”, a patented, affordable, natural fermented cider-based topical formulation. Through comprehensive in vitro analysis, the fermented extract demonstrated superior antioxidant efficacy, with an IC₅₀ value of 0.77 ± 0.03 mg/mL, significantly outperforming solvent and steam-distilled extracts, which showed IC₅₀ values of 2.49 ± 0.01 mg/mL and 4.11 ± 0.03 mg/mL, respectively. Notably, the nitric oxide scavenging activity of the fermented extracts was markedly higher than that of conventional extracts, with IC₅₀ values ranging from 1.12 ± 0.03 to 2.29 ± 0.03 mg/mL. Fermentation also enhanced total phenolic content (TPC), with mixed fruit extracts (pomegranate-beetroot, banana-papaya) reaching TPC levels of 2.43 ± 0.03 mg gallic acid equivalent/g, surpassing individual and conventionally processed samples. The study employed a Quality by Design approach to optimize fermentation conditions, achieving peak yields of gallic acid and TPC at 35 °C and 72 h, which further validates the process affordability. Under these conditions, the fermented extracts from pomegranate and beetroot demonstrated exceptional antimicrobial properties against E. coli, S. aureus, P. aeruginosa, P. acne, and M. furfur, with minimum inhibitory concentration values ranging from 0.25 mg/mL to 0.60 mg/mL, superior to those observed in conventionally extracted samples from pomegranate and beetroot. These findings highlight the efficacy of fermentation in enhancing bioactive compound availability, positioning FERMENZA as a potent fermented formulation for probable skin and hair-related cosmeceutical applications. Full article

The main objective of this research was to correlate the equilibrium solubility of sodium sulfadiazine in several {ethanol (EtOH, 1) + water (2)} mixtures reported in mass/volume and mass/mass percentages at different temperatures. Aqueous solubility of sodium sulfadiazine decreases almost linearly with decreasing temperature, but it decreases non-linearly with the addition of EtOH to water. Logarithmic solubility was adequately correlated with a bivariate model involving temperature and mixture composition. These solubility results were also well correlated with the Jouyban–Acree-based models. Moreover, an adapted version of the Jouyban–Acree model was used to represent the density of the saturated solvent mixtures at different temperatures. Furthermore, the apparent specific volumes of this drug at saturation were also calculated from densities of saturated solutions and cosolvent mixtures free of drug as well as from the respective mixture compositions. These findings provide valuable insights into the solubility and volumetric behavior of sodium sulfadiazine, which could be useful for pharmaceutical formulation and process optimization. Full article

A selective inhibitor of cyclooxygenase-2 (COX-2), Celecoxib (CEB), known for its anti-inflammatory properties, can exhibit polymorphism, with Form III often emerging as an undesired crystalline impurity during the green manufacturing process of the preferred Form I. Controlling the Form III content in the drug product is crucial, as different crystalline forms can impact drug bioavailability and therapeutic efficacy. This study presents a method to quantify the weight percentage of Form III in the bulk of CEB Form I by employing powder X-ray diffraction (PXRD). Initially, pure Form I and III of CEB were characterized using DSC, FTIR, and PXRD, supporting the method’s development. Binary mixtures, with varying ratios of CEB polymorphs Form I and Form III, were prepared and analyzed using continuous scans over an angular (2θ) range of 2–40. The calibration curve was constructed using 2θ unique peaks for Form I and Form III, respectively. Linear regression analysis exhibited a strong linear relationship within the weight ratio range of 1–20%. The developed method was validated to assess recovery, precision, ruggedness, limits of detection, and quantitation. These findings indicate that the method exhibits repeatability, sensitivity, and accuracy. The newly developed and validated PXRD method is applicable for quality control of CEB Form I produced through the green melt crystallization process by detecting low levels of Form III polymorphic impurity. This research significantly contributes to ensuring the clinical efficacy and manufacturing quality of Celecoxib by providing a reliable method for controlling polymorphic impurities. Full article

Lidocaine plays a significant role in postoperative analgesia by effectively reducing pain. However, due to its short half-life, it is challenging for lidocaine to achieve the desired duration of analgesia in clinical settings. Drug delivery systems can regulate the release rate over time, making them one of the most effective strategies for achieving sustained release. In this work, a multi-level drug delivery system was designed using hyaluronic acid-modified zeolitic imidazolate framework-8 (HA/ZIF-8) nanoparticles and injectable hydrogels composed of modified natural polymers. Lidocaine was incorporating into the modified ZIF-8 and uniformly dispersed within the hydrogel network. The dynamic light scattering (DLS) and Fourier transform infrared spectrometer (FTIR) results indicate the successful loading of lidocaine into ZIF-8, while the X-ray diffractometer (XRD) results confirm that the loading of lidocaine did not disrupt the crystal structure of ZIF-8. The coating of hyaluronic acid on ZIF-8 enhanced cell biocompatibility, with cell viability increasing by 89% at the same concentration. This multi-level drug delivery system can be injected through a 27-guage needle. In vitro release studies demonstrated a sustained release of lidocaine for more than 4 days and kinetic simulations aligned with the Bshakar model, indicating its potential for use in long-acting analgesic preparations. Full article

Lyophilization, or freeze-drying, is the default technique for the manufacture of solid-state formulations of therapeutic proteins. This established method offers several advantages, including improved product stability by minimizing chemical degradation, reduced storage requirements through water removal, and elimination of cold chain dependence. However, the lyophilization process itself presents limitations. It is a lengthy, batch-based operation, potentially leading to product inconsistencies and high manufacturing costs. Additionally, some proteins are susceptible to structural alterations during the freezing step, impacting their biological activity. This paper presents an alternative approach based on the co-precipitation of protein and excipients using an organic solvent. We explore the impact of various processing parameters on the viability of the formulation. We also provide an extensive characterization of proteins reconstituted from precipitated formulations and compare protein stability in solution and in lyophilized and precipitated solid formulations under long-term, accelerated, and stressed storage conditions. Full article

Poor solubility of many drugs, with ensuing low bioavailability, is a big challenge in pharmaceutical development. Nanosuspensions have emerged as a platform approach for long-acting injectables and solid dosages that enhance drug bioavailability. Despite improvements in nanosuspension preparation methods, ensuring nanosuspension stability remains a critical issue. Conventionally, synthetic and semi-synthetic polymers and surfactants are used in nanosuspension formulations. However, no polymer or surfactant group is universally applicable to all drugs. This fact, as well as their toxicity and side effects, especially if used in excess, have sparked the interest of researchers in the search for novel, natural stabilizers. The objective of this paper is to provide a comprehensive analysis of non-traditional natural stabilizers reported in the literature published over the last decade. First, physical stability and stabilization mechanisms are briefly reviewed. Then, various classes of non-traditional natural stabilizers are introduced, with particular emphasis on their stabilization potential, safety, and pharmaceutical acceptability. Wherever data were available, their performance was compared with the traditional stabilizers. Furthermore, the benefits and limitations of using these stabilizers are examined, concluding with future prospects. This review is expected to serve as a valuable guide for researchers and formulators, offering insights into non-traditional natural stabilizers in drug nanosuspension formulations. Full article

Celecoxib (CEL), a nonsteroidal anti-inflammation drug (NSAID), is categorized as a Class II drug (low solubility, high permeability) in the Biopharmaceutics Classification System (BCS). The aim of this study is to develop a novel formulation of CEL nanosuspensions in the form of dried powder for tableting or capsuling. In this study, CEL was formulated into nanosuspensions to improve its solubility. CEL nanosuspensions were prepared using the precipitation method followed by high-pressure homogenization. Drying of the nanosuspensions was performed by spray drying and freeze drying. We examined the impact of various formulation and processing parameters on the nanoparticles. The CEL nanoparticles were characterized by particle size analysis, differential scanning calorimetry (DSC), powder X-Ray diffraction (PXRD), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and dissolution tests. The choice of solvent, stabilizer, and surfactant appeared to have significant impacts on the crystallization and particle size and, consequently, the solubility of the CEL nanoparticles. CEL chemical stability was maintained throughout both drying processes. Both spray-dried and freeze-dried CEL nanosuspensions showed rapid dissolution profiles compared to raw CEL due to the nanosized particle dispersion with the presence of a lag phase. The freeze-dried nanosuspension showed a slight delay in the first 20 min compared to the spray-dried nanosuspension, after which dissolution progressed with a lag phase that represents aggregation. Full article

Background: The aqueous solubility of indomethacin, a poorly water-soluble anti-inflammatory drug, was enhanced by co-crystallization with co-formers. The co-crystals were characterized and compared by an X-ray diffraction (XRD) analysis, terahertz (THz) spectroscopy, and Fourier transform infrared (FT-IR) spectroscopy. Methods: Indomethacin co-crystals with either amides (saccharin, nicotine amide, and urea) or amino acids (lysine and histidine) as co-formers were prepared through the solvent evaporation method. The co-crystals were characterized by XRD, THz, and FT-IR analyses, followed by solubility tests to examine the solubility enhancement. Results: Both the XRD and THz analyses were capable of distinguishing co-crystals from physical mixtures; however, the THz spectra were relatively simpler and clearer than the XRD analysis. Furthermore, the solubility of indomethacin was successfully increased by two to three times that of pure indomethacin after co-crystallization with the above five co-formers. Conclusion: Five kinds of indomethacin co-crystals (with enhanced solubility) were successfully prepared and confirmed by the three spectroscopy techniques, XRD, THz, and FT-IR. The identification of co-crystals was achieved by a THz analysis, giving relatively simpler and clearer spectra with less noise. Hence, in addition to an XRD analysis, a THz analysis (a non-destructive, non-ionizing radiative, and relatively rapid measurement technique which is convenient and safe to use) is a good alternative method to characterize co-crystals. Full article