PurposeAssessment of the US FDA-issued WLs content is an educational tool that can be used in the continuous training program of community pharmacists in compounding pharmacies. The study was designed to critically assess FDA warning letters (WLs) issued to compounding pharmacies in 2017–2022 for violations of Current Good Manufacturing Practices (cGMP).MethodsContent analysis was used to evaluate WLs issued concerning (1) type of violations; (2) frequency of violations mentioned in the WLs; (3) specific evaluations of the deviations related to compounded sterile products, and (4) evaluation of corrective measures requested by the US FDA.ResultsA total of 141 WLs were evaluated. The main observed violations in the analyzed WLs were adulterated drug products (130), misbranded drugs (103), unapproved new drug products (42), failure to report adverse events (22), and failure to report drugs (11). Other violations were evaluated related to sterile product compounding with emphasis on personnel qualifications, quality control procedures, equipment, etc.ConclusionThe continuous issuance of WLs by the FDA indicates the need for compounding pharmacies become more vigilant to reduce the recurrence of the addressed violations through establishing adequate training/retraining programs. The analysis of issued WLs can serve as a learning tool to help improve compounding procedures, reduce the recurrence of these violations, and enhance patient safeguards.

PurposeThe phospholipids from plant origins play an important role in different techniques, especially in drug delivery applications. The purpose of this study is to investigate the effect of liposomes prepared from plant origin as a cheap source of lipids as drug carriers.MethodsSoy lecithin liposomes (SLP) were prepared and loaded with doxorubicin (DOX) to use as a drug delivery system. DOX was used as the model drug and DOX/SLP was successfully combined. The characteristics of these liposomes, zeta potential, size distribution, drug encapsulation efficiency (EE%), drug release, Fourier transform infrared (FTIR), and transmission electron microscopy (TEM) were checked followed by in vitro study. The cytotoxicity study by using free DOX and DOX/SLP is done on Mcf-7, human breast cancer as a cell line.ResultsThe optimal DOX/SLP formulation had a mean size of 342 nm, a negative zeta potential of −22.3 mV, the loaded DOX/SLP showed EE% (83.68%), and a drug release profile of 35 h, all are recorded. Cytotoxicity assay showed that the IC50 of DOX/SLP is smaller than that of free DOX.ConclusionThese results give evidence of the efficacy of using drug carriers from plant origin combined with drugs to increase the effective therapies against cancer medically and economically.Graphical Abstract

PurposeThe aim of present investigation was to develop oral jelly containing Baclofen-loaded chitosan microspheres for bioavailability enhancement, sustained release, and improved palatability. This is expected to improve the patient compliance by overcoming the difficulties in swallowing. Preformulation studies were performed for drug authentication.MethodsMicrospheres were prepared by emulsification thermal crosslinking method, and optimization of the parameters was done using 32 factorial design. The optimized formulation of microspheres was characterized for size, shape, drug content, in vitro drug dissolution, surface morphology, mucoadhesion, and micromeritic properties. The Baclofen microspheres were loaded in an oral jelly which possessed all the desired characteristics. In vivo pharmacokinetic study for the optimized batch and the marketed dosage form were performed in rabbits.ResultsThe in vivo result suggested that the oral bioavailability of jelly of Baclofen-loaded microspheres was 3.77 folds higher than that of the marketed formulation. Stability study of final optimized formulation indicated that the prepared formulation was stable at the storage conditions used.ConclusionThe developed formulation is a promising and paediatric patient compliant dosage form for improved safety and palatability of Baclofen.

PurposeCytarabine, an antimetabolite antineoplastic agent, has been used to treat acute myeloid leukemia. However, due to its short half-life, maintaining an optimal plasma concentration necessitates continuous intravenous administration, which may result in toxicity to healthy cells and tissues. The purpose of the current investigation was to design and optimize biodegradable poly (lactic acid) (PLA) nanoparticles (NPs) for improved delivery of cytarabine against acute myeloid leukemia.MethodThe NPs were prepared using a double emulsion evaporation technique. A 32 factorial design was employed to optimize the particle size and entrapment efficiency. The developed NPs were analyzed for particle size, polydispersity, and zeta potential using the dynamic light scattering (DLS) technique. The morphological analysis of NPs was conducted using transmission electron microscopy (TEM). The compatibility of drugs and excipients was examined using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. The entrapment efficiency of NPs was determined using an indirect method. In vitro drug release was carried out by dialysis bag method. The toxicity of NPs to leukemic cells (KG-1) was determined by MTT assay. The in vivo pharmacokinetic study was performed on rabbits.ResultsA total of nine formulations (PL1-PL9) were developed, with particle sizes ranging from 135.8 ± 1.7 to 295.0 ± 3.2 nm and entrapment efficiencies ranging from 46.27 ± 5.30 to 70.33 ± 0.80%. The optimized formulation (PL9) exhibited a reduced particle size (179.3 ± 1.9 nm), improved entrapment efficiency (56.13 ± 6.50%), spherical morphology, negative zeta potential (−17 mV), better compatibility between the polymer and drug, and conversion of cytarabine from a crystalline to an amorphous form in the formulation. The in vitro release pattern of cytarabine from NPs exhibited a first quick release (18–40%), followed by a sustained release for up to 48 h. The sustained release further enhanced the toxicity of cytarabine-loaded PLA NPs to KG-1 cell lines. The in vivo pharmacokinetics study showed a better pharmacokinetic profile of PL9 than the control.ConclusionThe study recommends that cytarabine-containing PLA NPs are a promising approach to overcome dose-limiting toxicity. The sustained release mechanism ensures maximum anti-leukemic effect and better pharmacokinetics.Graphical Abstract

PurposeThis study investigates the effects of heat annealing, drug, and lipid composition on the physical stability of solid lipid microparticles entrapped in hyaluronic acid.MethodsTristearin or glyceryl behenate lipid microparticles were loaded with bupivacaine or ropivacaine using high-shear homogenization at an elevated temperature. Half of each formulation underwent heat annealing at 60 °C for 24 h. Drug entrapment efficiency, in vitro drug release, differential scanning calorimetry, x-ray diffraction, and light microscopy were serially performed to characterize the stability of formulations over time.ResultsHeat annealed microparticles exhibited higher drug loss than non-annealed microparticles on Day 1 (e.g. 16.29% ± 0.83 vs. 1.14% ± 0.08 for tristearin-ropivacaine microparticles). After 6 months at room temperature, non-annealed ropivacaine microparticles exhibited lower drug loss than non-annealed bupivacaine microparticles (tristearin: 2.28% ± 0.69 vs. 10.06% ± 1.45; glyceryl behenate: 3.10% ± 0.10 vs. 20.24% ± 2.46). Non-annealed ropivacaine microparticles exhibited the longest drug release with 64.49% ± 5.44 (tristearin) and 59.23% ± 0.26 (glyceryl behenate) drug released at 80 h, respectively.ConclusionsNon-annealed, ropivacaine-containing formulations had the best shelf-life stability and exhibited the highest entrapment efficiencies after 6 months of storage compared to bupivacaine-containing and heat annealed formulations. Upon fabrication of the lipid microparticles, ropivacaine solidifies into a stable crystalline form. In contrast, bupivacaine initially solidifies into an amorphous form which is thermodynamically unstable and leads to drug leaching from the microparticles during storage. Ropivacaine is therefore a better candidate drug for a lipid microparticle entrapped in hyaluronic acid long-acting local anesthetic product.

PurposeThis research focuses on the development of a green synthesized chitosan-coated copper oxide nanocomposite gel for topical delivery. Due to the emergence of multidrug resistance and the lack of new antibiotics, bacterial infections, unintentional or otherwise, have become a serious disease that can be fatal. Under these circumstances, healthcare industries are under extreme pressure and in need of novel, multifunctional materials to combat human diseases. Nanocomposite-coated biopolymers are currently the most promising materials in the healthcare sector.MethodsThe green synthesized nanocomposite was characterized using zeta potential, particle size, X-ray diffraction (XRD), UV–visible spectroscopy, and FE-SEM analysis. The broth dilution method was used to determine the minimum inhibitory concentration (MIC) of the nanocomposite against gram-positive and gram-negative bacteria. The optimized nanocomposite was used for further development of antibacterial gel using different concentrations of Carbopol, and all formulations were subjected to physical evaluation such as pH, viscosity, spreadability, and extrudability.ResultsChitosan-coated copper oxide nanoparticles (CS-CuO) showed maximum absorption in the visible region at 416 nm. The XRD data showed characteristic diffraction patterns of the phases. The FE-SEM image of the synthesized nanocomposite showed a spherical shape. The MIC was 800 µg/ml.The average Z value, polydispersion index, and zeta potential obtained were found to be 235.7nm, 0.777, and 15 mV, respectively. The optimized formulation showed acceptable physical properties in terms of color, homogeneity, consistency, spreadability, and pH.ConclusionThe synthesized CS-CuO nanocomposite gel has antibacterial properties and is effective for topical application.

PurposeLittle attention has generally been given to non-sterile pharmaceutical manufacturing, because these products represent less microbial contamination risks compared to parenterals. Nevertheless, an extensive risk management program is required to prevent risk to patients and incidence of complaints or product recalls. Few scientific studies discuss on non-sterile production environment, which led to poor references for unreliable statistical approaches. The aim of this study was therefore to develop a statistical approach for microbial monitoring and limit calculation to be applied on non-sterile pharmaceutical industries, assessing two manufacturing facilities environments located in intertropical zones on different hemispheres.MethodsThe study evaluated a 2-year data of environmental monitoring active and passive air and surface microbiological recovery for both facilities using JMP™ as a statistical tool. Process and non-process rooms were evaluated to propose the statistical approach for monitoring and limit calculation.ResultsFit tests showed that microbiological environmental monitoring results for both facilities followed Gamma-Poisson distribution. Capability analyses performed against regulatory limits show that all data sub-groups were in control (Cpk > 1.3). Alert and action limits were proposed according to the actual distribution curve.ConclusionsThe study succeeded in developing a step-by-step statistical approach for assessing the EM program, which will support most non-sterile industries. The establishment of adequate limits is essential for false alarm prevention and for cost reduction with overreactions to in-control results. This study can also be extended to other process parameter control with similar distribution, expanding the applicability.

PurposeHerpes, a highly contagious viral infection caused by the herpes simplex virus, infects the face to any other body part of the skin, even the genital areas. Among the anti-herpes drugs, valacyclovir (VCV) possesses 55–70% oral bioavailability and more improved performance than acyclovir (15–20% oral bioavailability). However, a high daily intake of around 1 g is required. This work aimed to prepare a suitable carrier system to enhance bioavailability of VCV with reduced dose and dose-related side effects.MethodsThe processes of thin film hydration and reverse-phase evaporation were employed to synthesize liposomes encapsulating VCV, which were then subjected to basic characterizations such particle size and zeta potential. Moreover, FESEM and cryo-EM studies of the optimized formulation were also performed. FTIR spectroscopy was performed to detect incompatibility present if any between drug and excipients. The percentage drug loading and in vitro drug release were studied by UV–Visible spectrophotometer.ResultsThe results showed that the liposome vesicles were in nanosize range (140 ± 4.1 nm) with good colloidal stability (−62.75 ± 3.18 mV; the zeta potential) with appreciable drug loading capability. In vitro drug release studies revealed a biphasic release pattern, with initial burst release lasting up to 2 h and then continuous drug release. About 73% drug was released after 48 h.ConclusionBased on the findings, it was determined that VCV, a widely used drug for the treatment and prevention of viral infections in humans, may be formulated as a liposome for the successful treatment of herpes with a lower dose and improved bioavailability.Graphical Abstract

PurposeGefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has been authorized for the treatment of non-small lung cancer; however, its applications are not restricted. Instead, it can also be utilized for the treatment of other ailments, such as arthritis, breast cancer, and skin cancer. Their application is limited due to biopharmaceutical issues, as they belong to the second class of BCS and trigger first-pass metabolism.MethodsIn the present study, a gefitinib-phospholipid complex (GB-PC-90G) was developed using the solvent evaporation method through a job plot. The FTIR, DSC, and SEM morphologies confirmed and characterized the complexes. A dissolution study was performed at pH 1.2 and revealed improved drug release through complexation. The complex was loaded into a nanoemulsion (GB-PC90G@NE) using caproyl 90, Transcutol HP, and Tween 80 as the oil, surfactant, and co-surfactant, respectively. These parameters were optimized using Box–Behnken design (BBD) software, and the formulation underwent in vitro characterization.ResultsGlobule size and zeta potential for optimized batch were 165.6 nm and − 24.4 mV respectively. The SEM morphology indicated spherical nanoparticles. In vitro release at pH 7.4 showed the sustained release behavior of the drug from the nanoemulsion within 24 h compared to a non-complexed drug.Moreover, stability study data confirmed that complex-loaded nanoemulsions were stable for at least 3 months at 4 ℃ and 25 ℃.ConclusionFinally, it was concluded that GB-PC90G@NE enhanced gefitinib’s biopharmaceutical performance and hydrophilicity. In the future, this complex-loaded nanoemulsion will be subjected to ex vivo and in vivo studies to manage arthritis.

PurposeMercurial compounds are the classical Ayurvedic formulations extensively used in clinics. Kajjali or black sulphide of mercury, one of the primary mercurial compounds, is combined with herbs, metals, and minerals for internal use. Kajjali is prepared by mercury and sulphur, typically processed initially and then ground (Mardana) in equal proportions. The traditional method is manual, tedious, and time-consuming thus restricting mass production.MethodsThe present study demonstrates a simple but innovative grinding method using a modified ball mill for preparing Kajjali in lesser time. Triplicate batches were prepared by both methods, and finished products were assessed using classical Ayurvedic as well as modern physicochemical parameters.ResultsThe improvised mechanical method reduced manufacturing duration by 3.6 times and increased production by 3.5 fold. A lustreless, very fine black powder obtained by both methods depicted meta-cinnabar with excess sulphur by X-ray diffraction while scanning electron microscopy revealed comparable morphology. Dynamic light scattering technique showed particle size ranged between 90 and 500 nm while thermogravimetric analysis recorded degradation at around 190 and 600 °C, indicating oxidation of sulphur and sublimation of HgS, respectively. Fourier transform-infrared spectroscopy detected the presence of organic matter, viz. fats in Kajjali due to the use of cow’s ghee processed sulphur as raw material.ConclusionThe use of a modified ball mill was suitable for Kajjali preparation, enhanced productivity, and complied with good manufacturing practices. This innovative mechanical method yielded Kajjali of uniform particle size as compared to the manual method and can be enabled for automation.

PurposeCarotenoids are potent natural antioxidants with many important applications. Their nanodispersion formulations can solve problems that may limit their usage. In this study, we produced carotenoid nanodispersions from extracted lutein (nano-Lut), extracted β-carotene (nano-EBc), and synthetic β-carotene (nano-SBC).MethodsThe present study has quantitatively emphasized the physicochemical, antioxidant, and cytotoxic properties of free and nanodispersed formulations of lutein and β-carotene. The nanodispersions were characterized by spectral absorption, dynamic light scattering, and zeta potential. Antioxidant and cytotoxicity assays were conducted for free and their nanodispersed forms. The cytotoxicity of free carotenoids and their nanodispersions was conducted on HSF, VERO, and BNL cell lines.ResultsNano-Lut has the smallest mean particle size (185.2 ± 40.5 nm, PDI of 0.183 ± 0.01, and zeta potential of −28.6 ± 6.4 mV). Nano-SBc showed monomodal size distribution (220.5 ± 30.09 nm, PDI of 0.318 ± 0.03, and zeta potential of −12.1 ± 5.9 mV), while nano-EBc showed a bimodal size distribution (with a mean particle size of 498.3 ± 88.9 nm, PDI of 0.65 ± 0.08, and zeta potential of −39.7 ± 1.3 mV). All prepared nanodispersions showed less than 20% loss during the formulation process. Antioxidant assays showed that extracted lutein was the most active and synthetic β-carotene was the least. Cells showed higher tolerance for lutein and its nanodispersion than extracted or synthetic β-carotene either in free or nanodispersion forms.ConclusionsThe study proved that lutein in nanodispersed form possesses the smallest size, the highest antioxidant activity, and the lowest cytotoxicity among the tested formulations.

PurposeThe present investigation was aimed at preparing ketoconazole cocrystals using phenolic acid coformers.MethodThe slow solvent evaporation method was used to prepare ketoconazole cocrystal. The results of the DSC study, SEM study, and PXRD study confirmed the formation of a new crystalline phase.ResultThe results of FTIR and 1H NMR confirmed the possibility of H-bonding between the C = O group of PHBA and the CH2 group of ketoconazole. In the saturation solubility study performed at different pH solutions, the ketoconazole cocrystal solubility improvement was 2.28-fold in 0.1 N HCl, 7.25-fold in acetate buffer pH 4.5, 23.52-fold in phosphate buffer pH 6.8, and 15-fold in phosphate buffer pH 7.4 compared to pure ketoconazole. The in vitro dissolution study performed in the pH 1.2, pH 4.5, pH 6.8, and pH 7.4 dissolution media, the prepared cocrystal exhibited a significantly improved dissolution profile compared to the pure drug and physical mixture. The antifungal activity study confirmed that the cocrystals inhibited Candida albicans growth more than pure ketoconazole. These findings were supported by molecular docking results, which revealed that cocrystal produced less hepatotoxicity than pure ketoconazole in vitro.ConclusionMolecular docking results show cocrystal requires less binding energy and more binding affinity with sterol 14α-demethylase compared to pure ketoconazole and PHBA and has improved solubility and dissolution.Graphical Abstract

PurposeResveratrol (RSV) is a natural polyphenolic compound that has numerous biological effects. Owing to its poor bioavailability, only trace concentrations of RSV could be found at the site of action. Therefore, the present study was aimed at developing RSV-loaded nanospanlastics to improve its oral delivery and therapeutic activity.MethodsRSV-loaded nanospanlastics were prepared using the thin film hydration technique. The developed formulations were characterized via vesicular size (VS), polydispersity index (PDI), zeta potential (ZP) measurements, fourier transform infrared (FT-IR) spectroscopy analysis and transmission electron microscopy (TEM). In vitro release profile was carried out using dialysis bag diffusion technique. In vivo study was carried out using lipopolysaccharide (LPS)-induced endotoxicity model in mice to evaluate the formulations activity.ResultsThe results revealed the successful development of RSV-loaded nanospanlastics which exhibited EE% ranging from 45 to 85%, particle sizes ranging from 260.5 to 794.3 nm; negatively charged zeta potential (≤ − 20 mV) and TEM revealed their spherical shape. An in vitro release study showed biphasic pattern with sustained release of drug up to 24 h. In vivo results showed the superiority of RSV-loaded nanospanlastics over conventional niosomes in attenuating serum levels of liver and kidney functions (aspartate transaminase (AST), alanine transaminase (ALT), and creatinine) in LPS-induced endotoxic mice. Furthermore, both of them suppressed the elevated oxidative stress and inflammatory markers (malondialdehyde (MDA), nitric oxide (NO), and interleukin-1beta (IL-1β)) estimated in the liver and kidney tissues. However, the nanospanlastics showed a prevalence effect over conventional niosomes in kidney measurements and the histopathological examinations.ConclusionsThese findings reveal the potential of nanospanlastics in improving the oral delivery and therapeutic efficacy of RSV.

PurposeThe aim of this research work was to develop a mucoadhesive oro-gel–containing resveratrol loaded folate conjugated chitosan-lipidic nanoparticles (RES-FA-LP-NPs) for targeted delivery to oral squamous cell carcinoma (OSCC).MethodRES-FA-LP-NPs were prepared by hot homogenization followed by the ionic gelation method and were further incorporated in Carbopol® 971P gel. The in vitro cytotoxicity was assessed on folate receptor positive KB cell lines. The binding affinity of the folic acid (FA) ligand with the folate receptor was studied using Schrödinger, LLC, New York, NY, 2021.ResultsThe optimized unconjugated nanoparticles exhibited an average particle size of 107.5 nm ± 10.7 nm, polydispersity index (PDI) of 0.241 ± 0.024, zeta potential of 28.7 mV ± 0.9 mV, and encapsulation efficiency of 60 ± 3%. Surface folate conjugation of the nanoparticles increased the particle size to 149.9 nm ± 13.4 nm with PDI of 0.275 ± 0.041 and zeta-potential of 29.4 mV ± 1.4 mV. The RES-FA-LP-NP-loaded mucoadhesive oro-gel was found to have excellent mucoadhesive properties. The cumulative release from ex vivo diffusion studies on goat buccal mucosa at pH 6.8 was about 48.755 ± 8.627% and 64.802 ± 1.305% of resveratrol and folic acid respectively at the end of 8 h. The results of the cell culture study suggests that the developed RES-FA-LP-NPs were able to arrest OSCC (IC50 61.51 ± 2.70 μM/ml) at G0/G1 growth phase (58.08% apoptosis) of cell division. The binding interactions revealed that the ligand had excellent shape complementarity and a high binding affinity towards folate receptors.ConclusionPreliminary results state that the developed RES-FA-LP-NP-loaded gel can serve as a promising drug delivery system for the management of OSCC; however, more detailed investigations are needed to support the hypothesis.Graphical Abstract

PurposeInsulin is highly sensitive to an acidic pH medium and degrades faster. The encapsulation of insulin with chitosan (CS) particulates could partially solve this issue. Since the formation of particles involves different parameters, the unoptimized parameters and formulation result in unstable particles that exhibit a burst release in an acidic medium (pH = 1.20). On the other hand, the CS is poorly or partially soluble in PBS medium (pH = 7.40) and results in a limited insulin release. Therefore, the current study was conducted to prevent the insulin from degrading in an acidic medium and provide a sustained release in a PBS medium.MethodsIn this research, the chitosan-tripolyphosphate (CS-TPP) microparticles (MPs) were prepared and characterized in terms of size, PDI, and zeta potential. Furthermore, the effects of different parameters on the size, PDI, and zeta potential were determined. The experimental data for all these properties were validated using the artificial neural network (ANN) technique. The best conditions and formulation were used for insulin encapsulation and prepared MPs were characterized by FTIR, DSC, FESEM, and EDX. Afterwards, insulin release experiments were conducted in acidic (pH = 1.2) and PBS medium (pH = 7.4) for 8 h and release kinetics was conducted to estimate the release rate and mechanism of insulin release from different formulations.ResultsThe MPs prepared with optimized conditions such as CS concentration = 0.20% w/v, CS pH = 5.30, CS:TPP volume ratio = 3:1, mixing time = 1 h, and stirring speed = 1100 rpm possessed a particle size of 2.90 ± 0.33 μm and a high zeta potential of 55.65 ± 0.68 mV. These optimum conditions were further used for the formation of CS-insulin-TPP MPs that possessed a zeta potential of 25.41 ± 1.64 mV, 1.92 ± 0.07 μm size. Among different CS:TPP volume ratios, the MPs formed with 3:1 exhibited a cumulative insulin release of 55.78 ± 1.42% in 0.10 N HCl medium (pH = 1.20) and 60.79 ± 0.71% in the PBS medium (pH = 7.40). The insulin release occurred due to both diffusion and erosion mechanisms. The predominance of the mechanism for insulin release varied with time from diffusion to polymer chain relaxation.ConclusionsCurrent findings revealed that MPs prepared with optimized formulation and operating conditions protected the insulin from burst release in the acidic medium and provided a controlled release in the PBS medium. These MPs sufficiently controlled the insulin release rate and can be its good carrier.Graphical Abstract

PurposeHollow types of mesoporous silica have been extensively used as drug delivery carriers owing to their excessive drug loading competence in the interior void cavity as well as enhancement of solubility. The main aim of this study was to improve the solubility and dissolution rate of ARPZ, a class II drug, upon incorporation into mesoporous silica (SBA-15).MethodsARPZ was loaded in mesoporous silica using specific SBA-15 to solubilize by the wet impregnation method. The optimization was done via solubility and drug loading parameters. Characterization of the optimized formulation ARPZ-loaded SBA-15 (60%) (1.5:1 w/w) for possible molecular interaction between the ARPZ and silica was carried out by using FTIR, crystalline characteristics via PXRD, thermal analysis through DSC, and TGA, and pore size and surface area were determined by Brunauer–Emmett–Teller (nitrogen adsorption isotherm). Furthermore, an in vitro release study was examined by paddle-type dissolution apparatus (USP type II) in pH 1.2 buffer.ResultsThe optimized ARPZ-loaded SBA-15 (60%) showed a drug loading of 37–38% w/w. Incorporating the drug inside SBA-15 pores reduced the values of three parameters of empty SBA-15, (a) pore size from 5.21 to 4.19 nm, (b) pore volume from 0.652 to 0.178 cm3/g, and (c) specific surface area from 622.4 to 136.7 mg2/g. Crystalline ARPZ was converted to amorphous upon incorporation into pores of mesoporous silica. Optimized ARPZ-loaded SBA-15 (60%) exhibited more than 3 to fourfold enhancement in equilibrium solubility and dissolution after 15 min, respectively, compared to the pure ARPZ. The results showed an improvement in the solubility of ARPZ upon incorporation into pores of mesoporous silica SBA-15.ConclusionSBA-15 was found more suitable for the solubility enhancement of the poorly water-soluble drug ARPZ.Graphical Abstract

PurposeOver the past decade, successive outbreaks and epidemics of infectious diseases have challenged the emergency preparedness and response systems of global public health institutions, a context in which vaccines have become the centerpiece to strengthening global health security. Nevertheless, vaccine research and development (R&D) is a complex, lengthy, risky, uncertain, and expensive process. Alongside strict, time-consuming regulatory compliance, it takes multiple candidates and many years to register a new vaccine. This is certainly not welcome in a global health crisis such as the COVID-19 pandemic. Therefore, this study aims to understand the R&D paradigm shift in pandemic contexts and its impacts on the value chain of vaccine innovation.MethodsTo that end, this paper carried out a systematic literature review and meta-synthesis of 27 articles and reports (2011–2021) that addressed vaccine R&D in contexts of global health threats, disease outbreaks, epidemics, or pandemics.ResultsThe research findings are synthesized in a meta-model, which describes a fast-track R&D for pandemic contexts, its driving forces, innovations, mechanisms, and impacts in the value chain of vaccine innovation.ConclusionsThe study demonstrates that, in pandemic contexts, a fast-track R&D process based on close collaboration among regulators, industry, and academia and leveraging enabling technologies can drastically reduce the time required to bring safe, stable, and effective vaccines to market by an average of 11 years compared to the traditional R&D process. Furthermore, pharmacovigilance and rigorous monitoring of real-world evidence became critical to ensuring that quality and safe products were authorized for use during a pandemic.

PurposeIn recent years, the problem of drug abuse has emerged and is becoming more serious. Drug abuse can be secretly and illegally perpetuated by drug dealers and the general public. Therefore, a method to address this is required. The purpose of the study is to design the abuse deterrent formulations (ADFs) using various types of thermally deformed starch (TDS) for pseudoephedrine hydrochloride (PSE), a psychotropic drug.MethodsADFs were developed using a thermal denaturation method for four types of starch with crosslinker and lipid. The extraction of PSE was evaluated in ethyl alcohol (100% and 40% [v/v]), and performed the dissolution and in vitro release tests.ResultsA comparative experiment using four types of starch showed that PSE extraction was successfully suppressed. The extraction (%) of PSE from TDS-L2-ADFs (5 tablets (T) dose) showed the higher inhibition of extraction (71.1 ± 5.9%/2.8 ± 0.7%/54.0 ± 2.3%) than compared to those of SUDAFED® (99.5 ± 0.6%/99.1 ± 1.3%/99.0 ± 1.4%) in DW, ethyl alcohol (100% and 40% [v/v]), respectively, in stress condition (at 60 °C). Extraction (%) of PSE was significantly suppressed in ethyl alcohol (100% and 40% [v/v]). The in vitro PSE release profile of the TDS-L2 formulation (1 T and 5 T dose) showed sustain delayed release patterns compared to the SUDAFED® in the pH-shifting method.ConclusionFour types of starch-based formulations have been developed, and among them, thermal deformed natural starch formulations (TDS-L2-ADFs) have the highest drug abuse prevention ability and are expected to serve as the basis for future ADF development.

BackgroundGreen synthesis is a simple, inexpensive, and highly efficient method for the preparation of nanoparticles. In this study, ethanol extracts of Homalothecium sericeum (HOM) moss were used as reducing agents for the synthesis of biocompatible ruthenium nanoparticles (RuNPs). The ruthenium-based green synthesis method has not been used in any other work in the literature. UV–visible spectrophotometer (UV–Vis), Zetasizer, FTIR, and EDX-SEM were used to characterize the RuNPs synthesized by the green synthesis method, and their efficacy on cell viability was tested on HCT116 human colon cancer cells.MethodsUV spectroscopic measurements were used to study the release of HOM-RuNPs. Apoptosis was assessed by measuring protein expression of p53, Bax, and Bcl-2 by Western blotting. The presence of apoptosis was confirmed by double staining with Hoechst dye/propidium iodide under a fluorescence microscope. HOM-RuNPs were also tested for BCRP/ABCG2 expression to check for drug resistance.ResultsHOM-RuNPs with a size of 70–80 nm were found to be most effective at a dosage of 5.71 µg/ml and induced cell death by increasing the ratio of Bax/Bcl-2 and p53 expression. It was also shown to reduce multidrug resistance protein (ABCG2), suggesting that it may be useful against multidrug resistance.ConclusionRuthenium-based nanoparticles synthesized by a green synthesis technique may be a candidate for anticancer drugs in the pharmaceutical industry and deserve further attention for proof-of-concept studies.

PurposeChemical penetration enhancers (CPEs) are important in transdermal drug delivery (TDDD) formulations because they assist drugs in moving across the stratum corneum. Hydrocortisone (0.1% hydrocortisone, propylene glycol), oestradiol (0.045 mg estradiol/0.015 mg levonorgestrel, propylene glycol), and testosterone (2% testosterone, propylene glycol) are some examples of marketing TDDD formulations. As the transdermal route for drug administration becomes a safer and more appealing alternative to hypodermic needles, the search for new CPEs and their development becomes more important. Thus, the current work was directed toward the rapid identification of potent CPEs through the development of robust machine learning (ML) classification models.MethodsTwo large penetration enhancer (PE) data sets reported to date such as hydrocortisone (139 PEs) and theophylline (101 PEs) were used to build classification models. In the present investigation, a combination of feature selection methods, i.e., Boruta and Recursive Feature Elimination (RFE), and machine learning (ML) algorithms such as support vector machine (SVM), random forest (RF), and artificial neural network (ANN) were employed to classify the potent and weak penetration enhancers of hydrocortisone and theophylline. The tenfold cross-validation and Y-randomization methods were used to evaluate the prediction performance of the developed models.ResultsSignificant classification models were built for both data sets when the RFE method and RF algorithm were used. RF classifiers outperformed hydrocortisone and theophylline data sets with test set accuracy and Matthew’s correlation coefficient (MCC) greater than 0.78. Simultaneously, four important features required for the accurate classification of potent and weak PEs were identified, i.e., nHCsatu, minHCsatu, AATS4p, and GATS4e.ConclusionOur approach produced robust ML classification models that can be applied to prioritize PEs from large databases. Utilization of these ML models in virtual screening experiments could save time and effort in the identification of potential PEs.Graphical Abstract