Microneedles mediated-dermal delivery of Vitamin C: Formulation, characterization, cytotoxicity, and enhancement of stability.

Vitamin C (VIT C) is an antioxidant that prevents skin aging. Although dermal delivery is one of the most effective routes to transport VIT C to the skin, the impact of this route can be limited by the barrier function of the stratum corneum (SC). Additionally, VIT C rapidly oxidized and degraded under light and temperature. Therefore, this study provides an approach to utilizing microneedles (MNs) to improve the dermal delivery of VIT C and enhance its stability by incorporating a stabilizing system of ethylenediaminetetraacetic acid (EDTA) and sodium metabisulfite (Meta) within the MNs. Vitamin C microneedles (VIT C MNs) were fabricated using different biodegradable polymers and various concentrations of EDTA/Meta. VIT C MNs were evaluated for morphology, VIT C content, mechanical properties, dissolution rate, needles' insertion, physicochemical properties, ex vivo permeation, viscosity of VIT C polymeric solutions, cytotoxicity, and stability. The results showed that VIT C MNs were uniform and mechanically strong. The recovery of VIT C in MNs was 88.3-90.0 %. The dissolution rate of MNs was <30 min. The flux of VIT C varied based on the composition of MNs. VIT C MNs demonstrated safety against human dermal fibroblasts. VIT C MNs with EDTA/Meta (0.1/0.3 %) were stable under different storage conditions for two months. In conclusion, VIT C MNs were successfully developed using biodegradable polymers, and the stabilizing system (EDTA/META) provided a stable dermal delivery system for VIT C to protect skin from aging.

Design of colon-targeted drug delivery of dexamethasone: Formulation and in vitro characterization of solid dispersions.

Colon-targeted drug delivery continues to generate increasing attention for its prospects in treating inflammatory bowel disease (IBD). This study aimed to develop and evaluate colon-targeted solid dispersions of dexamethasone (DEX-SDs) in vitro to reduce its systemic exposure. This would ultimately improve the therapeutic efficacy of DEX while minimizing its adverse effects. Different DEX-SDs formulations were prepared utilizing Eudragit S100 (EU S100) and a combination of hydroxypropyl methyl cellulose (HPMC) and EU S100 to tune its drug release profile suitable for colonic delivery. The fabricated formulations were extensively characterized via Attenuated Total Reflectance - Fourier Transform Infrared Spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and polarized light microscopy (PLM). The different characterization techniques strongly suggest preparing solid solution-type solid dispersions of DEX with the other polymers (DEX-SDs). In addition, the in vitro dissolution of DEX-SDs was evaluated using two dissolution media (pH 1.2 and 7.4). The in vitro release of DEX-SDs was low in the acidic media and higher and sustained in the basic medium, leading to the conclusion that the developed DEX-SDs may represent an effective technology can overcome challenges related to poor drug solubility and bioavailability.

Transdermal Delivery System of Doxycycline-Loaded Niosomal Gels: Toward Enhancing Doxycycline Stability.

Doxycycline (DOX) is an antimicrobial agent that is susceptible to photosensitivity and thermal degradation. It addition, it causes gastrointestinal side effects when taken orally. Therefore, the development of alternative formulations is necessary to improve drug stability and promote patient compliance. The aim of the present study was to encapsulate DOX in niosomes as a nanocarrier to deliver DOX transdermally and enhance its stability in the formulation. DOX niosomes were prepared using nonionic surfactants, cholesterol, and dihexadecyl phosphate (DCP). After that, niosomes were characterized in terms of practical size (PS), zeta potential (ZP), morphology, and entrapment efficacy (EE%). DOX niosomal gels were then prepared using Carbopol and penetration enhancers (poly(ethylene glycol) 400 (PEG 400) and propylene glycol (PG)). The flux of DOX from the optimized formula was 322.86 µg/cm2/h over 5 h, which equates to 71.2% of DOX. Furthermore, neither the DOX niosomal gel (D3) nor the comparable blank niosomal gel had a negative influence on human dermal fibroblast (HDF) cells. The findings of the antimicrobial effectiveness of DOX niosomes indicated that the niosomal formulation improved the antibacterial activity of DOX against E. coli. Permeation studies demonstrated significantly higher DOX permeation when the niosomal gel was applied to rat skin, compared to the conventional gel. Permeability parameters such as flux and the permeability coefficient increased more than 10-fold using the niosomal gels compared with those of conventional gels. In conclusion, a new niosomal gel formulation could serve as an effective alternative for the commercially available form of DOX.

Topical gel formulations as potential dermal delivery carriers for green-synthesized zinc oxide nanoparticles.

This study aimed to incorporate green-synthesized zinc oxide nanoparticles (ZnO NPs), functionalized with polyethylene glycol (PEG) and linked to doxorubicin (DOX), into various topical gel formulations (hydrogel, oleogel, and bigel) to enhance their dermal delivery. The ZnO NPs were produced using the aqueous extract of the root hair of Phoenix dactylifera. The optimized green-synthesized ZnO NPs, PEGylated and conjugated to DOX, demonstrated a particle size below 100 nm, low polydispersity index, and zeta potential between - 11 and - 19 mV. The UV-Vis spectroscopy analysis confirmed characteristic absorption peaks at 351 and 545 nm for ZnO and DOX, respectively. The transmission electron microscope (TEM) images revealed well-dispersed spherical nanoparticles without aggregation. Additionally, ZnO NPs-loaded gels exhibited uniformity, cohesion, no phase separation, pseudoplastic flow, and viscoelastic properties. The in vitro release studies showed that DOX-PEG-ZnO NPs hydrogel released 99.5% of DOX after 5 h of starting the release. Moreover, the penetration of DOX-PEG-ZnO NPs through excised rat skin was visualized by TEM. In conclusion, the hydrogel formulation containing green-synthesized DOX-PEG-ZnO NPs holds great promise for dermal administration in skin cancer treatment. Furthermore, the release rate and skin penetration of DOX from gels were varied based on the type of gel matrix and corroborated with their corresponding rheological properties.

Impact of adding Mediterranean diet to aerobic and strengthening exercise program on pain, inflammation, and muscle performance in females with rheumatoid arthritis: a randomized controlled trial.

BACKGROUND: People with rheumatoid arthritis (RA) frequently use dietary interventions such as Mediterranean diet (MedDiet) and exercises to complement pharmacotherapy. OBJECTIVE: To investigate the effect of adding MedDiet to a designed exercise program on quadriceps and hamstrings muscles performance, pain, C-reactive protein (CRP), handgrip strength, bodyweight, and function in females with RA. METHODS: Sixty females were allocated randomly to the MedDiet plus exercise program (n = 30) or exercise program only (n = 30). The interventions continued for 6 months followed by 6 months of follow-up with no intervention. The primary outcome was the quadriceps and hamstrings muscles performance (agonist-antagonist ratio). The secondary outcomes were visual analog scale (VAS) for pain, CRP blood marker for inflammation, handheld dynamometer for handgrip strength, Health AssessmentQuestionnaire disability index (HAQ-DI) for function, and body weight. All outcomes were measured at baseline, 6-month post-intervention, and 12 months from baseline as a follow-up. RESULTS: The MedDiet group showed statistically significant improvements in all the measured outcomes than the control group (p < .05) after 6 and 12 months. After 6 months of intervention, the mean±SD for agonist-antagonist ratio, pain, and HAQ-DI were 84.59 ± 5.33 and 69.92 ± 5.56 (p < .001, ƞ2 = 0.65), 42.33 ± 8.98 and 54.33 ± 10.06 (p < .001, ƞ2 = 0.3), 1.13 ± 0.48 and 1.9 ± 0.59 (p < .001, ƞ2 = 0.34) in the MedDiet and control groups, respectively. CONCLUSION: Adding MedDiet to aerobic and strengthening exercise program improved quadriceps and hamstrings muscles performance, pain, functional ability, CRP, handgrip strength, and body weight. Consequently, Mediterranean diet should be considered as adjunctive therapy in treating females with RA.

Minoxidil Nanosuspension-Loaded Dissolved Microneedles for Hair Regrowth.

Minoxidil (MIN) is used topically to treat alopecia. However, its low absorption limits its use, warranting a new strategy to enhance its delivery into skin layers. The objective of this study was to evaluate the dermal delivery of MIN by utilizing dissolved microneedles (MNs) loaded with MIN nanosuspension (MIN-NS) for hair regrowth. MIN-NS was prepared by the solvent-antisolvent precipitation technique. The particle size of MIN-NS was 226.7 ± 9.3 nm with a polydispersity index of 0.29 ± 0.17 and a zeta potential of -29.97 ± 1.23 mV. An optimized formulation of MIN-NS was selected, freeze-dried, and loaded into MNs fabricated with sodium carboxymethyl cellulose (Na CMC) polymeric solutions (MIN-NS-loaded MNs). MNs were evaluated for morphology, dissolution rate, skin insertion, drug content, mechanical properties, ex vivo permeation, in vivo, and stability studies. MNs, prepared with 14% Na CMC, were able to withstand a compression force of 32 N for 30 s, penetrate Parafilm M® sheet at a depth of 374-504 µm, and dissolve completely in the skin within 30 min with MIN %recovery of 95.1 ± 6.5%. The release of MIN from MIN-NS-loaded MNs was controlled for 24 h. MIN-NS-loaded MNs were able to maintain their mechanical properties and chemical stability for 4 weeks, when kept at different storage conditions. The in vivo study of the freeze-dried MIN-NS and MIN-NS-loaded MNs proved hair regrowth on rat skin after 11 and 7 days, respectively. These results showed that MIN-NS-loaded MNs could potentially improve the dermal delivery of MIN through the skin to treat alopecia.

Development and characterization of magnetic hydrogels loaded with greenly synthesized iron-oxide nanoparticles conjugated with cisplatin.

A novel approach was devised to address the challenges in delivering cisplatin (CIS) for lung cancer treatment. This involved the development of a non-invasive hydrogel delivery system, aiming to minimize side effects associated with its administration. Using carbopol 971 (CP) and chitosan (CH) at varying ratios, the hydrogels were prepared and loaded with eco-friendly iron oxide nanoparticles (IONPs) conjugated to CIS. The physical properties, yield, drug loading, and cytotoxicity against lung cancer cell lines (A549) were assessed, along with hydrogel rheological properties and in vitro drug diffusion. Hydrogel A1 that composed of 1:1 of CP:CH hydrogel loaded with 100 mg IONPs and 250 µg CIS demonstrated distinctive properties that indicate its suitability for potential delivery. The loaded greenly synthesized IONPs@CIS exhibited a particle size of 23.0 nm, polydispersity index of 0.47, yield of 71.6%, with 88.28% drug loading. They displayed significant cytotoxicity (61.7%) against lung cancer cell lines (A549), surpassing free CIS cytotoxicity (28.1%). Moreover, they demonstrated shear-thinning behaviour, viscoelastic properties, and Fickian drug release profile over 24 h (flux 2.34 µg/cm2/h, and permeability 0.31 cm/h).

Breaking boundaries: the advancements in transdermal delivery of antibiotics.

Transdermal drug delivery systems (TDDS) for antibiotics have seen significant advances in recent years that aimed to improve the efficacy and safety of these drugs. TDDS offer many advantages over other conventional delivery systems such as non-invasiveness, controlled-release pattern, avoidance of first-pass metabolism. The objective of this review is to provide an overview on the recent advances in the TDDS of different groups of antibiotics including ß-lactams, tetracyclines, macrolides, and lincosamides, utilized for their effective delivery through the skin and to explore the challenges associated with this field. The majority of antibiotics do not have favorable properties for passive transdermal delivery. Thus, novel strategies have been employed to improve the delivery of antibiotics through the skin, such as the use of nanotechnology (nanoparticles, solid-lipid nanoparticles, nanoemulsions, vesicular carriers, and liposomes) or the physical enhancement techniques like microneedles and ultrasound. In conclusion, the transdermal delivery systems could be a promising method for delivering antibiotics that have the potential to improve patient outcomes and enhance the efficacy of drugs. Further research and development are still needed to explore the potential of delivering more antibiotic drugs by using various transdermal drug delivery approaches.

Development and Comparative Evaluation of Ciprofloxacin Nanoemulsion-Loaded Bigels Prepared Using Different Ratios of Oleogel to Hydrogels.

Nanoemulsions and bigels are biphasic delivery systems that can be used for topical applications. The aim of this study was to incorporate an oil-in-water ciprofloxacin hydrochloride nanoemulsion (CIP.HCl NE) into two types of bigels, Type I (oleogel (OL)-in-hydrogel (WH)) and Type II (WH-in-OL) to enhance drug penetration into skin and treat topical bacterial infections. Bigels were prepared at various ratios of OL and WH (1:1, 1:2, and 1:4). Initially, CIP.HCl NE was prepared and characterized in terms of droplet size, zeta potential, polydispersity index, morphology, and thermodynamic and chemical stability. Then CIP.HCl NE was dispersed into the OL or WH phase of the bigel. The primary physical stability studies showed that Type I bigels were physically stable, showing no phase separation. Whereas Type II bigels were physically unstable, hence excluded from the study. Type I bigels were subjected to microstructural, rheological, in vitro release, antimicrobial, and stability studies. The microscopic images showed a highly structured bigel network with nanoemulsion droplets dispersed within the bigel network. Additionally, bigels exhibited pseudoplastic flow and viscoelastic properties. A complete drug release was achieved after 4-5 h. The in vitro and ex vivo antimicrobial studies revealed that bigels exhibited antimicrobial activity against different bacterial strains. Moreover, stability studies showed that the rheological properties and physical and chemical stability varied based on the bigel composition over three months. Therefore, the physicochemical and rheological properties, drug release rate, and antimicrobial activity of Type I bigels could be modified by altering the OL to WH ratio and the phase in which the nanoemulsion dispersed in.

In Vitro and In Vivo Characterization of the Transdermal Gel Formulation of Desloratadine for Prevention of Obesity and Metabolic Syndrome.

Chronic use of antihistamines can induce abnormalities in lipid absorption with potential excessive accumulation of lipids in the mesentery that can lead to the development of obesity and a metabolic syndrome. The focus of the present work was to develop a transdermal gel formulation of desloratadine (DES) to prevent/reduce obesity and metabolic syndromes. Nine formulations were prepared to contain hydroxypropyl methylcellulose (2-3%), DES (2.5-5.0%), and Transcutol® (15-20%). The formulations were evaluated for cohesive and adhesive properties, viscosity, drug diffusion through synthetic and pig ear skin, and pharmacokinetics in New Zealand white rabbits. Drug permeation was faster through the skin compared to synthetic membranes. The drug had good permeation, as indicated by very short lag time (0.08-0.47 h) and high flux (59.3-230.7 µg/cm2.h). The maximum plasma concentration (Cmax) and area under the curve (AUC) of transdermal gel formulations were 2.4 and 3.2 fold that of the Clarinex tablet formulation. In conclusion, as indicated by the higher bioavailability, transdermal gel formulation of DES may decrease the dose of the drug, compared to commercial formulation. It has the potential to reduce or eliminate metabolic syndromes associated with oral antihistamine therapy.

Preparation and Characterization of Patch Loaded with Clarithromycin Nanovesicles for Transdermal Drug Delivery.

Clarithromycin (CLR), categorized as a Biopharmaceutical Classification System class II drug, has several gastrointestinal tract side effects and an extremely unpalatable bitter taste. The current study aimed to design transdermal patch-embedded CLR niosomes to overcome the aforementioned CLR-related challenges. Various niosomal formulations were successfully fabricated and characterized for their morphology, size, in vitro release, and antimicrobial efficacy. Subsequently, the CLR niosomes were loaded into transdermal patches using the solvent casting method. The polydispersity index of the niosomes ranged from 0.005 to 0.360, indicating the uniformity of the niosomes. The encapsulating efficiency (EE)% varied from 12 to 86%. The optimal Chol: surfactant ratio for drug release was found to be 0.5:1. In addition, the encapsulation of CLR into niosomal nanovesicles did not reduce the antibacterial activity of the CLR. The niosomal patch had a significantly higher permeability coefficient of CLR than the conventional patch. In addition to that, a shear-thinning behavior was observed in the niosomal gels before loading them into a niosomal patch. The flux (Jss) of the niosomal patch was significantly higher than the conventional patch by more than 200 times. In conclusion, niosome-based transdermal patches could be a promising method for the transdermal drug delivery of class II drugs and drugs experiencing GIT side effects.

Formulation and Evaluation of Azithromycin-Loaded Niosomal Gel: Optimization, In Vitro Studies, Rheological Characterization, and Cytotoxicity Study.

Several novel, innovative approaches for improving transdermal delivery of BCS class III drugs have been proposed. Despite their great aqueous solubility, BCS class III drugs have the drawback of limited permeability. The objective of the current work was to screen the suitability of niosomes as a nanocarrier in permeation enhancement of azithromycin (AZM) transdermal delivery. Niosomes were prepared by an ether injection method using a nonionic surfactant (Span 60) and cholesterol at different concentrations. The ζ potential (ZP), polydispersity index (PDI), and particle size (PS) of AZM-loaded niosomes were evaluated. The size of the niosomes was found to vary between 288 and 394 nm. The results revealed that the niosomes prepared in a ratio of 2:1 (Span 60: cholesterol) had larger vesicle sizes, but all of them were characterized by narrow size distributions (PDI <0.95). Niosomal gel was successfully prepared using different polymers. The appearance, pH, viscosity, and ex vivo drug release of niosomal gel formulations were all examined. The flow curves showed that the niosomal gel displayed lower viscosity values than its corresponding conventional gels. Niosomal and conventional gels exhibited a domination of the elastic modulus (G') over the viscous modulus (G″) (G'>G″) in the investigated frequency range (0.1-100 rad/s), indicating stable gels with more solid-like properties. Ex vivo skin permeation studies for the niosomal gel show 90.83 ± 3.19% of drug release in 24 h as compared with the conventional gel showing significantly lower (P < 0.001) drug release in the same duration (1.25 ± 0.12%). Overall, these results indicate that niosomal gel could be an effective transdermal nanocarrier for enhancing the permeability of AZM, a BCS class III drug. In conclusion, this study suggests that transdermal formulations of AZM in the niosomal gel were successfully developed and could be used as an alternative route of administration.

Microemulsions as Lipid Nanosystems Loaded into Thermoresponsive In Situ Microgels for Local Ocular Delivery of Prednisolone.

This study aimed to develop and evaluate thermoresponsive in situ microgels for the local ocular delivery of prednisolone (PRD) (PRD microgels) to improve drug bioavailability and prolong ocular drug residence time. Lipid nanosystems of PRD microemulsions (PRD-MEs) were prepared and evaluated at a drug concentration of 0.25-0.75%. PRD microgels were prepared by incorporating PRD-MEs into 10 and 12% Pluronic® F127 (F127) or combinations of 12% F127 and 1-10% Kolliphor®P188 (F68). PRD microgels were characterized for physicochemical, rheological, and mucoadhesive properties, eye irritation, and stability. Results showed that PRD-MEs were clear, miscible, thermodynamically stable, and spherical with droplet size (16.4 ± 2.2 nm), polydispersity index (0.24 ± 0.01), and zeta potential (-21.03 ± 1.24 mV). The PRD microgels were clear with pH (5.37-5.81), surface tension (30.96-38.90 mN/m), size, and zeta potential of mixed polymeric micelles (20.1-23.9 nm and -1.34 to -10.25 mV, respectively), phase transition temperature (25.3-36 °C), and gelation time (1.44-2.47 min). The FTIR spectra revealed chemical compatibility between PRD and microgel components. PRD microgels showed pseudoplastic flow, viscoelastic and mucoadhesive properties, absence of eye irritation, and drug content (99.3 to 106.3%) with a sustained drug release for 16-24 h. Microgels were physicochemically and rheologically stable for three to six months. Therefore, PRD microgels possess potential vehicles for local ocular delivery.

Beneath the Skin: A Review of Current Trends and Future Prospects of Transdermal Drug Delivery Systems.

The ideal drug delivery system has a bioavailability comparable to parenteral dosage forms but is as convenient and easy to use for the patient as oral solid dosage forms. In recent years, there has been increased interest in transdermal drug delivery (TDD) as a non-invasive delivery approach that is generally regarded as being easy to administer to more vulnerable age groups, such as paediatric and geriatric patients, while avoiding certain bioavailability concerns that arise from oral drug delivery due to poor absorbability and metabolism concerns. However, despite its many merits, TDD remains restricted to a select few drugs. The physiology of the skin poses a barrier against the feasible delivery of many drugs, limiting its applicability to only those drugs that possess physicochemical properties allowing them to be successfully delivered transdermally. Several techniques have been developed to enhance the transdermal permeability of drugs. Both chemical (e.g., thermal and mechanical) and passive (vesicle, nanoparticle, nanoemulsion, solid dispersion, and nanocrystal) techniques have been investigated to enhance the permeability of drug substances across the skin. Furthermore, hybrid approaches combining chemical penetration enhancement technologies with physical technologies are being intensively researched to improve the skin permeation of drug substances. This review aims to summarize recent trends in TDD approaches and discuss the merits and drawbacks of the various chemical, physical, and hybrid approaches currently being investigated for improving drug permeability across the skin.

Preparation and Evaluation of Polyvinylpyrrolidone Electrospun Nanofiber Patches of Pioglitazone for the Treatment of Atopic Dermatitis.

Nanofibers have many promising biomedical applications. They can be used for designing transdermal and dermal drug delivery systems. This project aimed to prepare and characterize polyvinylpyrrolidone-based nanofibers as a dermal and transdermal drug delivery system using pioglitazone. Pioglitazone is an oral antidiabetic drug. In addition, it can act as an inflammatory process modulator, making it a good candidate for managing different skin inflammatory conditions such as atopic dermatitis, skin ulcers, and diabetic foot wound healing. Several nanofiber formulations were prepared using the electrospinning method at different drug loadings, polyvinylpyrrolidone concentrations, and flow rates. A cast film with the exact composition of selected nanofiber formulations was prepared as a control. Nanofibers were characterized using a scanning electron microscope to calculate the diameter. Fourier-transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and powder X-ray diffraction were performed for physical and biochemical characterizations. In vitro release, drug loading efficiency, and swelling studies were performed. Ex vivo permeation studies were performed using Franz diffusion cells with or without applying a solid microneedle roller. Round uniform nanofibers with a smooth surface were obtained. The diameter of nanofibers was affected by the drug loading and polymer concentration. Fourier-transform infrared spectra showed a potential physical interaction between the drug and the polymer. According to X-ray diffraction, pioglitazone existed in an amorphous form in prepared nanofibers, with partial crystallinity in the casted film. Nanofibers showed a higher swelling rate compared to the casted film. The drug dissolution rate for nanofibers was 2.3-folds higher than the casted films. The polymer concentration affected the drug dissolution rate for nanofibers; however, drug loading and flow rate did not affect the drug dissolution rate for nanofibers. The application of solid microneedles slightly enhances the total amount of drug permeation. However, it did not affect the flux of the drug through the separated epidermis layer for pioglitazone. The drug permeation flux in nanofibers was approximately five times higher than the flux of the casted film. It was observed that pioglitazone is highly retained in skin layers. Graphical abstract.

Recent exploration of nanoemulsions for drugs and cosmeceuticals delivery.

BACKGROUND: Nanoemulsions (NEs) have been explored as nanocarriers for the delivery of many drugs and cosmeceuticals. The extraordinary expansion of using NEs is due to their capability to conquer the main challenges of conventional delivery systems such as short residence time with low patient acceptance, poor stability, low aqueous solubility, permeability, and hence bioavailability. METHODS: This review recapitulated the most recent pharmaceutical and cosmeceutical applications of NEs as effective delivery nanocarriers. The outputs of our research studies and the literature review on the latest NEs applications were assessed to highlight the NEs components, preparations, applications, and the improved quality and elegance of the used product. RESULTS: NEs are stable submicronic translucent dispersions with narrow droplet size distribution. They exhibited excellent ability to efficiently encapsulate therapeutics of diverse nature of drugs and cosmeceuticals. NE formulations showed superiority over conventional delivery approaches with overabundances of advantages through different routes of administration. This novel technology exhibited better aesthetic appeal, higher bioavailability, and a longer duration compared to the conventional delivery systems. CONCLUSION: This novel technology holds promise for different therapeutics fields. However, the success of NEs use advocated the development of robust formulations, proper choice of equipment, ample process characterization, and assurance of their efficacy, stability, safety and cosmetic appeal.

Development of stable amorphous solid dispersion and quantification of crystalline fraction of lopinavir by spectroscopic-chemometric methods.

This study aimed to improve the dissolution of the poorly soluble drug lopinavir (LPV) by preparing amorphous solid dispersions (ASDs) using solvent evaporation method. The ASD formulations were prepared with ternary mixtures of LPV, Eudragit® E100, and microcrystalline cellulose (MCC) at various weight ratios. The ASDs were subjected to solid-state characterization and in vitro drug dissolution testing. Chemometric models based on near infrared spectroscopy (NIR) and NIR-hyperspectroscopy (NIR-H) data were developed using the partial least squares (PLS) regression and externally validated to estimate the percent of the crystalline LPV in the ASD. Initially, the solid-state characterization data of ASDs showed transformation of the drug from crystalline to amorphous. Negligible fraction of crystalline LPV was present in the ASD (3%). Compared to pure LPV, ASDs showed faster and higher drug dissolution (<2% vs. 60.3-73.5%) in the first 15 min of testing. The ASD was stable against crystallization during stability testing at 40 °C/75% for a month. In conclusion, the prepared ASD was stable against devitrification and enhance the dissolution of LPV.

Optimism Bias, Pessimism Bias, Magical Beliefs, and Conspiracy Theory Beliefs Related to COVID-19 among the Jordanian Population.

The outbreak of the novel SARS-CoV-2 virus has an enormous impact on health. People's views about the virus impact public health efforts to mitigate the pandemic. In this study, we measured misconceptions toward coronavirus in the Jordanian population; 2,544 participants from the Jordanian population completed an online survey. Questions in the survey addressed misconceptions divided into four categories: optimism bias, pessimism bias, magical beliefs, and conspiracy theory beliefs. Questions were evaluated on a Likert scale, and average/median scores for each category were evaluated ("one" high misconception to "five" low misconception). Overall, the most common misconceptions involved conspiracy theory beliefs (2.68 ± 0.83), whereas the least common involved magical beliefs (2.25 ± 0.75). Females had more misconceptions than males (2.52 versus 2.47, P = 0.04). Participants who had attended a lecture on coronavirus, had a higher level of education, worked in a medical field, lived in urban area, or resided in Amman or northern Jordan had fewer misconceptions about SARS-CoV-2/COVID-19 (2.64, 2.34, 2.33, 2.50 and 2.50 versus 2.53, 2.73, 2.72, 2.64, and 2.66, respectively, P < 0.001). The use of social media appeared to be an important factor influencing the likelihood of false beliefs (2.61 versus 2.38, P < 0.001). Understanding of the factors influencing public perceptions surrounding the SARS-CoV-2/COVID-19 pandemic will help public health authorities improve public understanding and compliance with public health recommendations directed at combatting the virus, including the use of surgical masks, thorough handwashing, and avoiding close contact. These messages will be better received by the public through correcting misconceptions surrounding COVID-19.

3D-printing of lopinavir printlets by selective laser sintering and quantification of crystalline fraction by XRPD-chemometric models.

The objectives of this study were to develop and characterize amorphous lopinavir (LPV) printlets and to the quantify crystalline fraction of LPV in the printlets by X-ray powder diffraction (XRPD)-chemometric models. Amorphous printlets (4.5 mm diameter × 3 mm height) of various LPV concentrations were fabricated by selective laser sintering (SLS) 3D technique. The printlets were characterized for physicochemical properties. The XRPD data in conjunction with chemometric method were used to quantify the crystalline fraction of the drug. The LPV content in the printlets was 95.2-100.9%, disintegration time was < 2 min, and dissolution was fast (>90% of LPV was dissolved in < 30 min). The porosity of the printlets increased with an increase in the LPV percentage. The differential scanning calorimetry (DSC) and XRPD data of the printlets demonstrated that the majority of LPV was present in amorphous form. The XRPD-chemometric models showed good linearity and low root mean squared error, standard error, and bias. Models validation showed that the actual values of crystalline and amorphous fractions of the drug were close to the predicted values. These results demonstrated the feasibility of fabricating amorphous printlets by SLS method, and the application of the XRPD-chemometric models to quantify low fractions of crystalline drug in the 3D formulations if they are formed due to process or environment related variables.

Gelation and rheological characterization of Carbopol® in simulated gastrointestinal fluid of variable chemical properties.

Carbopol® is a hydrophilic polymer commonly used in the preparation of oral controlled-release matrix tablets. These matrices are subjected to dissolution testing to investigate the rate and mechanism of drug release. The rate of drug release from these matrices is influenced by the viscoelastic properties of the gel layer formed upon hydration and surrounded tablet core. This study evaluates the gelation behavior and rheological characterization of Carbopol® in dispersion media, of varied chemical properties, commonly used in dissolution testing. The rheological properties of Carbopol® polymer underwent gelation were determined using a controlled-stress rheometer. Carbopol® gelation was not found in simulated gastric fluid of low pH (1.2-5.0) and simulated intestinal fluid of pH (5.0-6.5) during fasted (Fa) and fed (Fe) conditions. However, in water and at high pH (6.8-7.8), gelation occurred in phosphate buffers of high buffering capacity (ß). Furthermore, no gelation was found in sodium chloride solutions of different ionic strengths (µ). These results highlight the importance of investigating the gelation behavior and rheological characterization of Carbopol® in dispersion media prior to dissolution testing. These preliminary studies can give an insight on the formation/absence of the gel layer around Carbopol® matrices which is responsible for controlling the release of drugs.