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Micromachines Apr 2024Non-steroidal anti-inflammatory piroxicam (PRX) is a poorly water-soluble drug that provides relief in different arthritides. Reducing the particle size of PRX increases...
Non-steroidal anti-inflammatory piroxicam (PRX) is a poorly water-soluble drug that provides relief in different arthritides. Reducing the particle size of PRX increases its bioavailability. For pediatric, geriatric, and dysphagic patients, oral dispersible systems ease administration. Moreover, fast disintegration followed by drug release and absorption through the oral mucosa can induce rapid systemic effects. We aimed to produce an orodispersible lyophilizate (OL) consisting of nanosized PRX. PRX was solved in ethyl acetate and then sonicated into a poloxamer-188 solution to perform spray-ultrasound-assisted solvent diffusion-based nanoprecipitation. The solid form was formulated via freeze drying in blister sockets. Mannitol and sodium alginate were applied as excipients. Dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) were used to determine the particle size. The morphology was characterized by scanning electron microscopy (SEM). To establish the crystallinity, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used. A disintegration and in vitro dissolution test were performed. DLS and NTA presented a nanosized PRX diameter. The SEM pictures showed a porous structure. PRX became amorphous according to the XRPD and DSC curves. The disintegration time was less than 1 min and the dissolution profile improved. The final product was an innovative anti-inflammatory drug delivery system.
PubMed: 38675343
DOI: 10.3390/mi15040532 -
Pharmaceutics Apr 2024Oral colon delivery systems based on a dual targeting strategy, harnessing time- and microbiota-dependent release mechanisms, were designed in the form of a...
Oral colon delivery systems based on a dual targeting strategy, harnessing time- and microbiota-dependent release mechanisms, were designed in the form of a drug-containing core, a swellable/biodegradable polysaccharide inner layer and a gastroresistant outer film. High-methoxyl pectin was employed as the functional coating polymer and was applied by spray-coating or powder-layering. Stratification of pectin powder required the use of low-viscosity hydroxypropyl methylcellulose in water solution as the binder. These coatings exhibited rough surfaces and higher thicknesses than the spray-coated ones. Using a finer powder fraction improved the process outcome, coating quality and inherent barrier properties in aqueous fluids. Pulsatile release profiles and reproducible lag phases of the pursued duration were obtained from systems manufactured by both techniques. This performance was confirmed by double-coated systems, provided with a Kollicoat MAE outer film that yielded resistance in the acidic stage of the test. Moreover, HM pectin-based coatings manufactured by powder-layering, tested in the presence of bacteria from a Crohn's disease patient, showed earlier release, supporting the role of microbial degradation as a triggering mechanism at the target site. The overall results highlighted viable coating options and in vitro release characteristics, sparking new interest in naturally occurring pectin as a coating agent for oral colon delivery.
PubMed: 38675167
DOI: 10.3390/pharmaceutics16040508 -
Pharmaceutics Mar 2024Mucoadhesive microparticles for oromucosal drug delivery offer several advantages, including intimate contact with the mucosa, delivery to less accessible regions,...
Mucoadhesive microparticles for oromucosal drug delivery offer several advantages, including intimate contact with the mucosa, delivery to less accessible regions, extended residence time, sustained drug release, reduced irritation, and improved patient compliance. In this study, pullulan was used to prepare mucoadhesive spray-dried microparticles for delivering benzydamine hydrochloride (BZH) to oral mucosa. The BZH-pullulan spray-dried microparticles had a mean size of <25 μm with an angle of repose values between 25.8-36.6°. Pullulan markedly extended drug-release time to >180 min, ~9 times greater than the duration (i.e., 20 min) reportedly achieved by chitosan. Kinetic analysis showed the drug-release rate was concentration dependent and jointly controlled by drug diffusion and polymer chain relaxation. Further, pullulan was mucoadhesive and was able to retain up to 78.8% w/w of microencapsulated gold nanoparticle probes at the mucosal membrane. These data strongly suggest that BZH-pullulan microparticles have great potential for oromucosal drug delivery, by providing elongated residence time in situ and sustained drug release for the treatment of local diseases.
PubMed: 38675121
DOI: 10.3390/pharmaceutics16040460 -
Pharmaceutics Mar 2024Enzalutamide (ENZ), marketed under the brand name Xtandi as a soft capsule, is an androgen receptor signaling inhibitor drug actively used in clinical settings for...
Enzalutamide (ENZ), marketed under the brand name Xtandi as a soft capsule, is an androgen receptor signaling inhibitor drug actively used in clinical settings for treating prostate cancer. However, ENZ's low solubility and bioavailability significantly hinder the achievement of optimal therapeutic outcomes. In previous studies, a liquid self-nanoemulsifying drug delivery system (L-SNEDDS) containing ENZ was developed among various solubilization technologies. However, powder formulations that included colloidal silica rapidly formed crystal nuclei in aqueous solutions, leading to a significant decrease in dissolution. Consequently, this study evaluated the efficacy of adding a polymer as a recrystallization inhibitor to a solid SNEDDS (S-SNEDDS) to maintain the drug in a stable, amorphous state in aqueous environments. Polymers were selected based on solubility tests, and the S-SNEDDS formulation was successfully produced via spray drying. The optimized S-SNEDDS formulation demonstrated through X-ray diffraction and differential scanning calorimetry data that it significantly reduced drug crystallinity and enhanced its dissolution rate in simulated gastric and intestinal fluid conditions. In an in vivo study, the bioavailability of orally administered formulations was increased compared to the free drug. Our results highlight the effectiveness of solid-SNEDDS formulations in enhancing the bioavailability of ENZ and outline the potential translational directions for oral drug development.
PubMed: 38675118
DOI: 10.3390/pharmaceutics16040457 -
Dentistry Journal Apr 2024Soft drinks may have a deleterious effect on dental health due to a high titratable acidity and a low pH that could be sufficient to induce tooth demineralization. The...
Soft drinks may have a deleterious effect on dental health due to a high titratable acidity and a low pH that could be sufficient to induce tooth demineralization. The use of oral care products immediately after acidic challenge may diminish the erosive potential of soft drinks. We assessed the effect of oral care foams and a spray on salivary pH changes after exposure to Coca-Cola in young adults. Thirty-three consenting eligible patients were recruited in this double-blind, randomized, crossover study performed in six visits. Baseline examination included unstimulated salivary flow rate, stimulated salivary buffer capacity, and the simplified oral hygiene index (OHI-S) assessment. Salivary pH and time for pH recovery were registered after exposure to Coca-Cola alone or that followed by the application of each of the studied products (an oral foam containing hydroxyapatite and probiotics, an oral foam containing amino fluoride, an alkaline oral spray, and tap water). Thirty-two patients completed the entire study protocol and were included in the final analysis. The mean minimum salivary pH and the mean oral clearance rate after rinsing with Coca-Cola were 6.3 and 27 min, respectively. Further rinsing with any one of the tested solutions, including tap water, resulted in a significant improvement in these parameters. When the pH curves were plotted, the oral care products demonstrated a lower area under the curve that differed significantly from the area under the curve for Coca-Cola; tap water did not differ significantly from Coca-Cola and oral care products. Minimum salivary pH correlated positively with salivary buffer capacity and salivation rate, while salivary clearance correlated with OHI-S plaque scores. In conclusion, the effect of oral care foams and a spray on minimum salivary pH and salivary clearance after exposure to Coca-Cola did not differ significantly among the tested products and tap water. Trial registration NCT06148662. Funding: none.
PubMed: 38668005
DOI: 10.3390/dj12040093 -
Analytical and Bioanalytical Chemistry Jun 2024Metformin (MET) and sitagliptin (STG) are widely used as the first-line and long-term oral hypoglycemic agents for managing type 2 diabetes mellitus (T2DM). However, the...
Metformin (MET) and sitagliptin (STG) are widely used as the first-line and long-term oral hypoglycemic agents for managing type 2 diabetes mellitus (T2DM). However, the current lack of convenient and rapid measurement methods poses a challenge for individualized management. This study developed a point-of-care (POC) assay method utilizing a miniature mass spectrometer, enabling rapid and accurate quantification of MET and STG concentrations in human blood and urine. By combining the miniature mass spectrometer with paper spray ionization, this method simplifies the process into three to four steps, requires minimal amounts of bodily fluids (50 μL of blood and 2 μL of urine), and is able to obtain quantification results within approximately 2 min. Stable isotope-labeled internal standards were employed to enhance the accuracy and stability of measurement. The MS/MS responses exhibited good linear relationship with concentration, with relative standard deviations (RSDs) below 25%. It has the potential to provide immediate treatment feedback and decision support for patients and healthcare professionals in clinical practice.
Topics: Humans; Sitagliptin Phosphate; Metformin; Point-of-Care Systems; Hypoglycemic Agents; Limit of Detection; Tandem Mass Spectrometry; Diabetes Mellitus, Type 2; Mass Spectrometry; Reproducibility of Results
PubMed: 38642098
DOI: 10.1007/s00216-024-05281-1 -
AAPS PharmSciTech Apr 2024Oral candidiasis is a fungal infection affecting the oral mucous membrane, and this research specifically addresses on a localized treatment through fluconazole-loaded...
Oral candidiasis is a fungal infection affecting the oral mucous membrane, and this research specifically addresses on a localized treatment through fluconazole-loaded ibuprofen in situ gel-based oral spray. The low solubility of ibuprofen is advantageous for forming a gel when exposed to an aqueous phase. The 1% w/w fluconazole-loaded in situ gel oral sprays were developed utilizing various concentrations of ibuprofen in N-methyl pyrrolidone. The prepared solutions underwent evaluation for viscosity, surface tension, contact angle, water tolerance, gel formation, interface interaction, drug permeation, and antimicrobial studies. The higher amount of ibuprofen reduced the surface tension and retarded solvent exchange. The use of 50% ibuprofen as a gelling agent demonstrated prolonged drug permeation for up to 24 h. The incorporation of Cremophor EL in the formulations resulted in increased drug permeation and exhibited effective inhibition against Candida albicans, Candida krusei, Candida lusitaniae, and Candida tropicalis. While the Cremophor EL-loaded formulation did not exhibit enhanced antifungal effects on agar media, its ability to facilitate the permeation of fluconazole and ibuprofen suggested potential efficacy in countering Candida invasion in the oral mucosa. Moreover, these formulations demonstrated significant thermal inhibition of protein denaturation in egg albumin, indicating anti-inflammatory properties. Consequently, the fluconazole-loaded ibuprofen in situ gel-based oral spray presents itself as a promising dosage form for oropharyngeal candidiasis treatment.
Topics: Fluconazole; Candidiasis, Oral; Oral Sprays; Ibuprofen; Antifungal Agents; Candida albicans; Microbial Sensitivity Tests; Glycerol
PubMed: 38641711
DOI: 10.1208/s12249-024-02804-y -
Expert Opinion on Pharmacotherapy Apr 2024Gastroparesis is a chronic disorder characterized by decreased gastric emptying and presents with nausea, vomiting, and abdominal pain which impacts patients' quality of... (Review)
Review
INTRODUCTION
Gastroparesis is a chronic disorder characterized by decreased gastric emptying and presents with nausea, vomiting, and abdominal pain which impacts patients' quality of life greatly. The treatment modalities available for gastroparesis have been expanding over the past 2 decades. Currently, there are multiple options available for gastroparesis, albeit with only one FDA-approved medication until June 2021.
AREAS COVERED
We review the different treatments available for gastroparesis and discuss the recently FDA-approved intranasal formulation of metoclopramide. This nasal spray guarantees metoclopramide absorption within 15 min of application bypassing first pass metabolism in the liver and overcoming the limitations of the oral formulation not passing into the small intestine for absorption because of a gastroparetic stomach or a patient unable to take the oral metoclopramide because of nausea and vomiting.
EXPERT OPINION
We now find ourselves in an oasis after spending many years in a 'desert' regarding pharmacologic therapies available for gastroparesis. The expansion of the research involving dopamine receptor antagonists and delving into alternative mechanisms of alleviating gastroparesis symptoms has been crucial in the landscape of gastroparesis. This is especially true as our knowledge of gastroparesis has proven that simply improving gastric emptying does not necessarily translate to clinical improvement.
Topics: Humans; Administration, Intranasal; Dopamine Antagonists; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Metoclopramide; Quality of Life
PubMed: 38629943
DOI: 10.1080/14656566.2024.2344646 -
In Vitro Analysis of Outcome Differences Between Repairing and Replacing Broken Dental Restorations.Cureus Mar 2024Objective In light of several advancements and considerations in endodontic dentistry, there still remains a need to comprehensively evaluate the outcome disparities...
Objective In light of several advancements and considerations in endodontic dentistry, there still remains a need to comprehensively evaluate the outcome disparities between repairing and replacing broken dental restorations. This study aims to compare the effectiveness of repairing dental restorations versus replacing them, focusing on how each method affects the structural strength and longevity of the restorations. Methods The study included 60 freshly removed human maxillary premolars. Initial processing involved rigorous washing, descaling, and polishing of the teeth. To ensure preservation, the specimens were stored in sterile, distilled water. To occlude the root canals, a self-hardening composite resin was used, and the roots were coated with two coats of clear nail polish to prevent moisture penetration. A 245 carbide bur attached to a high-speed dental handpiece with air and water spray cooling produced standardized Class II cavities on the occluso-proximal surfaces. Each cavity had a buccolingual breadth of 2 mm, an occluso-cervical length of 4 mm, and a gingival boundary that was 1 mm coronal to the cement-enamel junction. Following this preparation, the teeth were randomly separated into three groups (Group A, Group B, and Group C), each containing 20 teeth. Results Our analysis showed that teeth with entirely replaced restorations had a higher average fracture resistance than those with repaired restorations. However, the difference in fracture resistance between the repair and replacement groups for each type of material was not statistically significant. Conclusion Based on the findings, repairing a dental restoration can be a conservative and less invasive alternative to a full replacement without a significant compromise in the restoration's ability to withstand fracture. Therefore, dental professionals might consider full restoration as a viable option, taking into account the need to preserve dental tissue as well as the restoration's durability and structural integrity.
PubMed: 38618331
DOI: 10.7759/cureus.56071 -
Journal of Oral Biology and... 2024Maintenance of the quality and hygiene of maxillofacial prosthesis allows to maintain the health of the residual tissues. Sampling of the maxillofacial prostheses has...
UNLABELLED
Maintenance of the quality and hygiene of maxillofacial prosthesis allows to maintain the health of the residual tissues. Sampling of the maxillofacial prostheses has relieved presence of microbial colonization on silicone surfaces. Cleaning procedures of maxillofacial silicones are done using mechanical means or using adjunctive with chemical means. Cleaning with a 2-4% chlorhexidine gluconate spray or dipping in solution for a minute and then washing under running water can sufficiently condition to reduce the amount of bacterial contamination. Due to rising microorganism resistance and fewer adverse effects, phytoextracts appear to be a viable option. Additionally, the use of excipients derived from plants is provides new opportunities for the pharmaceutical industry into the creation of innovative pharmaceutical products that are sustainable.
AIM
To evaluate and compare the leaf extracts of and 0.2% chlorhexidine gluconate (CHX) on disinfection of maxillofacial silicone material surface contaminated with (
METHODS
Of the 150 maxillofacial silicone elastomer silicone samples, 75 samples were contaminated with and 75 with . The contaminated disc was rolled on blood agar and pre-disinfection Colony Forming Units (CFU) were evaluated followed by subjecting the discs to disinfection protocols. The contaminated discs with and were disinfected using leaf extracts, leaf extracts and 0.2% CHX for 10 min. Post-disinfection CFUs were evaluated by rolling the disc on blood agar. The results were tabulated and analysed using dependent -test, one-way ANOVA and Tukeys multiple posthoc procedure.
RESULTS
Pair-wise comparison of pre-and post-disinfection log CFU counts of gave a statistical significance between 0.2% CHX and leaf extract. No statistically significant results were found between 0.2% CHX and . Pair wise comparison of the log CFU from pre-disinfection to post-disinfection of gave a statistical significance between all the three groups.
CONCLUSIONS
In the present study leaf extract leaf extract have shown significant reduction in CFU of both the organisms. 0.2% CHX showed the most CFU reduction post disinfection of maxillofacial silicone material surface contaminated followed by leaf extracts and leaf extracts Given the limitations of the current research, leaf extract leaf extract can be used as an alternative for disinfection of maxillofacial silicone prosthesis.
PubMed: 38618184
DOI: 10.1016/j.jobcr.2024.03.014