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Journal of Controlled Release :... Jun 2024In vitro-In vivo correlation (IVIVC) is a main focus of the pharmaceutical industry, academia and the regulatory sectors, as this is an effective modelling tool to...
In vitro-In vivo correlation (IVIVC) is a main focus of the pharmaceutical industry, academia and the regulatory sectors, as this is an effective modelling tool to predict drug product in vivo performance based on in vitro release data and serve as a surrogate for bioequivalence studies, significantly reducing the need for clinical studies. Till now, IVIVCs have not been successfully developed for in situ forming implants due to the significantly different in vitro and in vivo drug release profiles that are typically achieved for these dosage forms. This is not unexpected considering the unique complexity of the drug release mechanisms of these products. Using risperidone in situ forming implants as a model, the current work focuses on: 1) identification of critical attributes of in vitro release testing methods that may contribute to differences in in vitro and in vivo drug release from in situ forming implants; and 2) optimization of the in vitro release method, with the aim of developing Level A IVIVCs for risperidone implants. Dissolution methods based on a novel Teflon shape controlling adapter along with a water non-dissolvable glass fiber membrane (GF/F) instead of a water dissolvable PVA film (named as GF/F-Teflon adapter and PVA-Teflon adapter, respectively), and an in-house fabricated Glass slide adapter were used to investigate the impact of: the surface-to-volume ratio, water uptake ratio, phase separation rate (measured by NMP release in 24 h post injection in vitro or in vivo), and mechanical pressure on the drug release patterns. The surface-to-volume ratio and water uptake were shown to be more critical in vitro release testing method attributes compared to the phase separation rate and mechanical pressure. The Glass slide adapter-based dissolution method, which allowed for the formation of depots with bio-mimicking surface-to-volume ratios and sufficient water uptake, has the ability to generate bio-relevant degradation profiles as well as in vitro release profiles for risperidone implants. For the first time, a Level A IVIVC (rabbit model) has been successfully developed for in situ forming implants. Release data for implant formulations with slightly different PLGA molecular weights (MWs) were used to develop the IVIVC. The predictability of the model passed external validation using the reference listed drug (RLD), Perseris®. IVIVC could not be developed when formulations with different PLGA molar ratios of lactic acid to glycolic acid (L/G) were included. The present work provides a comprehensive understanding of the impact of the testing method attributes on drug release from in situ forming implants, which is a valuable practice for level A IVIVC development.
PubMed: 38936743
DOI: 10.1016/j.jconrel.2024.06.058 -
Indian Journal of Dental Research :... Jan 2024To comparatively evaluate the effect of normal saline gel and ozonated saline-ozonated gel (ozone therapy) on pain, inflammation, soft tissue, and crestal bone loss in... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
AIMS
To comparatively evaluate the effect of normal saline gel and ozonated saline-ozonated gel (ozone therapy) on pain, inflammation, soft tissue, and crestal bone loss in dental implant surgery.
METHODS AND MATERIAL
Forty adult patients scheduled to undergo implant were randomized into two groups: Twenty patients (n = 20) received ozone therapy and controls (n = 20) received normal saline and gel during implant placement. Inflammation and pain were noted at days 1 and 7 and 3 month intervals by estimating C-reactive protein (CRP) levels and assessing visual analogue scale (VAS) scores. At 3 months, soft tissue outcomes were noted in terms of plaque index, gingival index, and pocket depth, while crestal bone loss was noted via a radiograph.
RESULTS
Mean CRP levels were significantly higher in the control group as compared to that in the case group on day 1 and day 7 follow-ups (P < 0.05). Mean VAS scores for pain were also lower in the case group as compared to the control group at all follow-ups, but the difference was significant statistically only at day 1 (P = 0.061). The plaque index was significantly lower in the case group as compared to the control group (P = 0.011) at final follow-up. No significant difference between two groups was observed for crestal bone loss.
CONCLUSIONS
Ozone therapy during implant placement was effective in reduction of pain, systemic inflammation, and plaque deposition in dental implant patients.
Topics: Humans; Ozone; Gels; Male; Female; Adult; Middle Aged; C-Reactive Protein; Saline Solution; Dental Implants; Dental Plaque Index; Alveolar Bone Loss; Periodontal Index; Pain Measurement; Dental Implantation; Inflammation
PubMed: 38934740
DOI: 10.4103/ijdr.ijdr_591_23 -
Journal of Food and Drug Analysis Jun 2024Aflatoxin B, a major global food safety concern, is produced by toxigenic fungi during crop growing, drying, and storage, and shows increasing annual prevalence. This...
Aflatoxin B, a major global food safety concern, is produced by toxigenic fungi during crop growing, drying, and storage, and shows increasing annual prevalence. This study aimed to detect aflatoxin B in chili samples using ATR-FTIR coupled with machine learning algorithms. We found that 83.6% of the chili powder samples were contaminated with Aspergillus and Penicillium species, with aflatoxin B levels ranging from 7.63 to 44.32 μg/kg. ATR-FTIR spectroscopy in the fingerprint region (1800-400 cm) showed peak intensity variation in the bands at 1587, 1393, and 1038 cm, which are mostly related to aflatoxin B structure. The PCA plots from samples with different trace amounts of aflatoxin B could not be separated. Vibrational spectroscopy combined with machine learning was applied to address this issue. The logistic regression model had the best F1 score with the highest %accuracy (73%), %sensitivity (73%), and %specificity (71%), followed by random forest and support vector machine models. Although the logistic regression model contributed significant findings, this study represents a laboratory research project. Because of the peculiarities of the ATR-FTIR spectral measurements, the spectra measured for several batches may differ, necessitating running the model on multiple spectral ranges and using increased sample sizes in subsequent applications. This proposed method has the potential to provide rapid and accurate results and may be valuable in future applications regarding toxin detection in foods when simple onsite testing is required.
Topics: Capsicum; Spectroscopy, Fourier Transform Infrared; Aflatoxin B1; Food Contamination; Aspergillus; Powders; Penicillium
PubMed: 38934688
DOI: 10.38212/2224-6614.3497 -
Archivio Italiano Di Urologia,... Jun 2024The management of chronic prostatitis/ chronic pelvic pain syndrome type III (CP/CPPS) has been always considered complex due to several biopsychological factors...
OBJECTIVE
The management of chronic prostatitis/ chronic pelvic pain syndrome type III (CP/CPPS) has been always considered complex due to several biopsychological factors underlying the disease. In this clinical study, we aimed to evaluate the efficacy of the treatment with Palmitoylethanolamide, Epilobium and Calendula extract in patients with CP/CPPS III.
MATERIALS AND METHODS
From June 2023 to July 2023, we enrolled 45 consecutive patients affected by CP/CPPS type III in three different institution. We included patients aged between 18 and 75 years with symptoms of pelvic pain for 3 months or more before the study, a total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score ≥ 12 point and diagnosed with NIH category III, according to 4-glass test Meares-Stamey test. Patients were then allocated to receive rectal suppositories of PEA, Epilobium and Calendula, 1 suppository/ die for 1 month. All patients have been tested with standard urinalysis in order to assess urinary leukocytes (U-WBC). The primary endpoint of the study was the reduction of NIHCPSI. The secondary outcomes were the change of peak flow, post-void residual (PVR), IIEF-5, VAS score, PSA and decrease of U-WBC.
RESULTS
A total of 45 patients concluded the study protocol. At baseline, the median age of all the patients included in the cohort was 49 years, the median PSA was 2.81 ng/ml, the median NIH-CPSI was 18.55, the median IIEF-5 was 18.27, the median U-WBC was 485.3/mmc, the median VAS score was 6.49, the median PVR was 26.5 ml and the median peak flow was 16.3 ml/s. After 1 month of therapy we observed a statistically significant improvement of NIH-CPSI, U-WBC, PSA, IIEF-5, peak flow, PVR and VAS.
CONCLUSIONS
In this observational study, we showed the clinical efficacy of the treatment with PEA, Epilobium and Calendula, 1 suppository/die for 1 month, in patients with CP/CPPS III. The benefits of this treatment could be related to the reduction of inflammatory cells in the urine that could imply a reduction of inflammatory cytokines. These results should be confirmed in further studies with greater sample size.
Topics: Humans; Male; Middle Aged; Adult; Prostatitis; Suppositories; Amides; Aged; Palmitic Acids; Treatment Outcome; Young Adult; Ethanolamines; Plant Extracts; Epilobium; Calendula; Adolescent; Chronic Disease; Pelvic Pain
PubMed: 38934521
DOI: 10.4081/aiua.2024.12582 -
Current Pediatric Reviews Jun 2024An off-label medication involves the use of an approved drug for an unapproved indication, population, route of administration, or dosage.The physiological state of...
Awareness, Practice, and Views of Pediatricians, General Physicians, and Pharmacists about Prescribing Off-label Medication in Pediatric Patients in Eastern Province, Saudi Arabia.
BACKGROUND
An off-label medication involves the use of an approved drug for an unapproved indication, population, route of administration, or dosage.The physiological state of children differs from that of adults, making the adult formulation potentially dangerous to children. Off-label prescribing is quite common in children due to challenges in the development of pediatric formulations. The current study was conducted to determine the awareness, practice, and views of pediatricians, general physicians, and pharmacists about prescribing Off-label medication to pediatric patients in Eastern Province, Saudi Arabia.
METHODS
A cross-sectional study based on a questionnaire was conducted among pediatricians, general physicians, and pharmacists (clinical and community) in Eastern Province, Saudi Arabia. Statistical analysis was conducted using the data exported from Google Forms (Mountain View, California, USA) and Microsoft Excel (Version 2016) and then exported into Statistical Package for Social Sciences (SPSS) version 26.0 (IBM, Inc., Armonk, NY, USA). Chi-square was deemed suitable. The level of significance was set at 0.05.
RESULTS
Among the study participants, 53(35.09%) were pharmacists, followed by 24(15.89%) others, 22(14.565) pediatricians, 19(12.58%) other specialists, 17(11.25%) general physicians, and 16(10.59%) were clinical pharmacist. About 73(48.34%) described the definition of off-label correctly. About 114(75.49%) believed that parents and guardians must be informed about off-label medicine prescribed to their children. About 52(34.43%) had concerns about the safety of the medication, and 98(64.90%) believed they should be tested in pediatrics during clinical trials. Further, 97(64.23%) considered themselves not enough knowledgeable about off-label medications. The barriers reported by the participants were as follows: 89(58.945%) said lack of information resources, 71(47.01%) said lack of training, 56(37.08%) said lack of information on the safety of excipients used in pediatrics, 47(31.12%) said lack of formulary, 44(29.13%) said lack of guidelines, and 58(5.29%) said lack of information related to the safety of excipient concentration in pediatrics. The proportion of healthcare professionals who agreed that excipients in adult medication may be harmful to pediatrics was 103(68.21%). The drugs most often prescribed as off-label were paracetamol 54(21.68%), followed by Phenobarbital 35(14%), and Amoxicillin 33(13.25%).
CONCLUSION
There are a considerable number of healthcare professionals unaware of the description of off-label medication. The majority have concerns over the safety and efficacy of the off-label drugs and believe that most frequently used off-label drugs in pediatrics must be tested in pediatrics during clinical trials. In addition, excipient safety data are of considerable importance to ensure off-label drug safety in pediatrics, who believe their knowledge is inadequate and need proper guidelines and training on this issue.
PubMed: 38934287
DOI: 10.2174/0115733963298903240614072717 -
F1000Research 2023Strawberry is a fruit with a high antioxidant capacity due to its richness in phenolic compounds that suffer a rapid post-harvest deterioration. Spray drying is an...
Strawberry is a fruit with a high antioxidant capacity due to its richness in phenolic compounds that suffer a rapid post-harvest deterioration. Spray drying is an alternative to reduce losses; however, these powders present problems of instantanisation, making it necessary to implement agglomeration processes. During storage, powdered food products can undergo a series of changes in their amorphous state from a product initially in a vitreous state to a gummy state, where all properties are substantially modified due to the increased mobility of water in the matrix. The research objective was to evaluate the storage stability (6 months) of a fluidized bed agglomerated strawberry powder mixture at three temperatures (15, 25 and 25°C), a controlled environment at 65% relative moisture, and PET laminated film bags as packaging. Moisture, water activity, and compacted density, Carr and Hausner indices, solubility, hygroscopicity, wettability, angle of repose, antioxidant capacities, total phenols, anthocyanins, vitamin C, color (CIE-Lab) and particle size were monitored. ANOVA showed statistically significant differences (p<0.05) for all dependent variables concerning storage time; storage temperature had no significant effect on S, ABTS, DPPH and Hu. The time-temperature interaction during storage had no significant effect (p>0.05) on S, ABTS, DPPH, Hu and L. The agglomerate showed moisture and aw values that confer excellent stability against deterioration reactions; it retained good fluidity, low cohesiveness, and retentions above 50% for antioxidant capacity, 76% for total phenols, 39% for anthocyanins, and 40% for vitamin C; particle size was retained during the evaluation. The color was only affected in the 35°C treatment from the fifth month onwards. The study will serve as a tool for the determination of the shelf life of the chipboard once the critical values of the attributes selected as predictors of shelf life are defined.
Topics: Fragaria; Antioxidants; Powders; Food Storage; Phenols; Temperature; Spray Drying; Particle Size; Anthocyanins; Ascorbic Acid
PubMed: 38933490
DOI: 10.12688/f1000research.138509.1 -
Viruses Jun 2024Porcine reproductive and respiratory syndrome virus (PRRSV) presents a significant threat to the global swine industry. The development of highly effective subunit...
Porcine reproductive and respiratory syndrome virus (PRRSV) presents a significant threat to the global swine industry. The development of highly effective subunit nanovaccines is a promising strategy for preventing PRRSV variant infections. In this study, two different types of ferritin (Ft) nanovaccines targeting the major glycoprotein GP5, named GP5m-Ft and (Bp-IVp)-Ft, were constructed and evaluated as vaccine candidates for PRRSV. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) demonstrated that both purified GP5m-Ft and (Bp-IVp)-Ft proteins could self-assemble into nanospheres. A comparison of the immunogenicity of GP5m-Ft and (Bp-IVp)-Ft with an inactivated PRRSV vaccine in BALB/c mice revealed that mice immunized with GP5m-Ft exhibited the highest ELISA antibody levels, neutralizing antibody titers, the lymphocyte proliferation index, and IFN-γ levels. Furthermore, vaccination with the GP5m-Ft nanoparticle effectively protected piglets against a highly pathogenic PRRSV challenge. These findings suggest that GP5m-Ft is a promising vaccine candidate for controlling PRRS.
Topics: Animals; Porcine respiratory and reproductive syndrome virus; Ferritins; Mice, Inbred BALB C; Swine; Mice; Antibodies, Viral; Antibodies, Neutralizing; Nanoparticles; Porcine Reproductive and Respiratory Syndrome; Viral Vaccines; Viral Envelope Proteins; Female; Interferon-gamma; Nanovaccines
PubMed: 38932282
DOI: 10.3390/v16060991 -
Pharmaceutics Jun 2024Etomidate is a general anesthetic that has shown good hemodynamic stability without significant cardiovascular or respiratory depression. Despite several kinds of dosage...
Etomidate is a general anesthetic that has shown good hemodynamic stability without significant cardiovascular or respiratory depression. Despite several kinds of dosage forms having been reported for this drug, formulation types are very limited in clinical practice, and brain-targeted formulations for this central nervous system (CNS) drug have been rarely reported. Moreover, studies on the biocompatibility, toxicity, and anesthetic effects of the etomidate preparations in vivo were inadequate. The present study was to develop lactoferrin-modified liposomal etomidate (Eto-lip-LF) for enhanced drug distribution in the brain and improved anesthetic effects. Eto-lip-LF had good stability for storage and hemocompatibility for intravenous injection. Compared with the non-lactoferrin-containing liposomes, the lactoferrin-modified liposomes had notably enhanced brain-targeting ability in vivo, which was probably realized by the binding of transferrin with the transferrin and lactoferrin receptors highly distributed in the brain. Eto-lip-LF had a therapeutic index of about 25.3, higher than that of many other general anesthetics. Moreover, compared with the commercial etomidate emulsion, Eto-lip-LF could better achieve rapid onset of general anesthesia and rapid recovery from anesthesia, probably due to the enhanced drug delivery to the brain. The above results demonstrated the potential of this lactoferrin-modified liposomal etomidate to become an alternative preparation for clinical general anesthesia.
PubMed: 38931926
DOI: 10.3390/pharmaceutics16060805 -
Pharmaceutics Jun 2024Propranolol hydrochloride, a non-cardio-selective beta blocker, is used to treat several conditions in children, including hypertension, arrhythmias, hyperthyroidism,...
Propranolol hydrochloride, a non-cardio-selective beta blocker, is used to treat several conditions in children, including hypertension, arrhythmias, hyperthyroidism, hemangiomas, etc. Commercial liquid formulations are available in Europe and the US, but they have disadvantages, such as limited stability, bitter taste, and the need for multiple daily doses due to the drug's short half-life. Considering these limitations, controlled-release solid formulations, such as microparticles, may offer a better solution for pediatric administration. The main objective of this study was to formulate an encapsulation system for propranolol hydrochloride, based on sodium alginate and other polysaccharide polymers, to control and prolong its release. Microparticles were prepared using the ionotropic gelation method, which involves instilling a polymer solution into a solution of gelling ions via the extrusion technique. Physicochemical characterization was conducted by assessing the entrapment efficiency, drug loading, swelling index, microparticle size, rheological properties, and surface tension. In order to improve the characteristics of the tested microparticles, selected formulations were coated with chitosan. Further experimental work included differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) analysis, and SEM imaging. This in vitro release study showed that chitosan-coated microparticles demonstrate favorable properties, suggesting a novel approach to formulating pediatric dosage forms, although further optimization is necessary.
PubMed: 38931909
DOI: 10.3390/pharmaceutics16060788 -
Pharmaceutics May 2024Paediatric infectious diseases contribute significantly to global health challenges. Conventional therapeutic interventions are not always suitable for children, as they... (Review)
Review
Paediatric infectious diseases contribute significantly to global health challenges. Conventional therapeutic interventions are not always suitable for children, as they are regularly accompanied with long-standing disadvantages that negatively impact efficacy, thus necessitating the need for effective and child-friendly pharmacotherapeutic interventions. Recent advancements in drug delivery technologies, particularly oral formulations, have shown tremendous progress in enhancing the effectiveness of paediatric medicines. Generally, these delivery methods target, and address challenges associated with palatability, dosing accuracy, stability, bioavailability, patient compliance, and caregiver convenience, which are important factors that can influence successful treatment outcomes in children. Some of the emerging trends include moving away from creating liquid delivery systems to developing oral solid formulations, with the most explored being orodispersible tablets, multiparticulate dosage forms using film-coating technologies, and chewable drug products. Other ongoing innovations include gastro-retentive, 3D-printed, nipple-shield, milk-based, and nanoparticulate (e.g., lipid-, polymeric-based templates) drug delivery systems, possessing the potential to improve therapeutic effectiveness, age appropriateness, pharmacokinetics, and safety profiles as they relate to the paediatric population. This manuscript therefore highlights the evolving landscape of oral pharmacotherapeutic interventions for leading paediatric infectious diseases, crediting the role of innovative drug delivery technologies. By focusing on the current trends, pointing out gaps, and identifying future possibilities, this review aims to contribute towards ongoing efforts directed at improving paediatric health outcomes associated with the management of these infectious ailments through accessible and efficacious drug treatments.
PubMed: 38931836
DOI: 10.3390/pharmaceutics16060712