Biopharmaceutical Modeling of Food Effect─Exploring the Role of Dietary Fat.

In preclinical drug discovery, simple fraction absorbed calculators are exceptionally valuable tools to better understand the potential limitations to drug absorption and how different formulation approaches may address them. These tools often struggle to accurately capture the impact of food on drug absorption. One possible reason for this is that these models overlook the potential role of dietary fat in altering drug absorption. Herein, we present a novel approach to incorporate the fat content from diet within an absorption model as an additional set of particles that can accumulate in the mucus and act to reduce the effective thickness of the unstirred water layer. Using this approach, we demonstrate improved model prediction on the extent of food effect for a range of marketed compounds comparing two historical absorption models and the new model developed in this work using published food effect data for 21 marketed compounds. We extended this work to investigate each model's ability to predict the reported food effect across a range of dose levels for Venetoclax. Finally, we investigate the new model's capability to predict food effect in both low-fat and high-fat fed states and compare these predictions to the two historical models using three model compounds: Albendazole, Pazopanib, and Venetoclax.

Compatibility of Nonoriginal Abutments With Implants: Evaluation of Microgap at the Implant-Abutment Interface, With Original and Nonoriginal Abutments.

PURPOSE: The purpose of this study was to evaluate the fit of nonoriginal abutments to implants at the implant abutment junction. MATERIALS AND METHODS: Twenty titanium implants from a single manufacturer were randomly divided into 2 groups of ten each. Ten titanium premachined original abutments (group I) and ten titanium premachined nonoriginal abutments (from different manufacturer-group II) were connected to the implants with the recommended manufacturer torque level and then embedded into autopolymerizing clear acrylic resin blocks. After overnight curing, these blocks were vertically sectioned using water jet sectioning machine and evaluated under scanning electron microscope following the sequential cleaning procedures. The microgap at the implant-abutment interface for all the samples was measured using pixel counting software and subjected to statistical analysis using nonparametric Mann-Whitney U test. RESULTS: The mean microgap at the implant-abutment interface at the external, middle, and internal points was 1.597, 1.399, and 1.831 µm, respectively, for group I and 2.395, 2.488, and 3.339 µm, respectively, for group II samples. Nonparametric Mann-Whitney U test showed statistically significant difference between 2 groups at the midpoint for the nonoriginal abutments compared with the original ones. CONCLUSION: Within the limitations of the study, the mean microgap at the implant-abutment interface at the platform level at the external, middle, and internal points for both original abutments and nonoriginal abutments was found to be within clinically acceptable limits.

Comparative Evaluation of the Masking Ability of Lithium Disilicate Ceramic with Different Core Thickness on the Shade Match of Indirect Restorations over Metallic Substrate: An In vitro Study.

PURPOSE: The purpose of this in vitro study was to comparatively evaluate the masking ability of lithium disilicate ceramic with different core thickness on the shade match of indirect restorations over metallic substrate. MATERIALS AND METHODS: A total of 30 heat pressed lithium disilicate ceramic discs of low translucency were fabricated with diameter 10mm and thickness of 1 mm, 1.3 mm and 1.6mm with each thickness consisting of 10 samples to be used in the study. Thirty Ni-Cr metal discs of diameter 10mm were used to simulate metallic substrates .The colour difference of the lithium disilicate ceramic disc before and after cementation were measured using CIE LAB system. RESULTS: The mean colour difference (ΔE) of Group I,Group II, Group III before cementation with the Ni-Cr metal discs was 17.32,13.01 and 11.73 respectively. The mean colour difference (ΔE) of Group I,Group II, Group III after cementation with the Ni-Cr metal discs was 16.32,12.10, 11.05 respectively. CONCLUSION: The mean colour difference of the three groups were found to be more than the clinically acceptable perceptibility threshold (ΔE < 3.3) indicative of reduced masking ability of all the three groups of ceramic discs over metallic substrate used in this study.

Comparative Evaluation of the Antimicrobial Efficacy of Three Immersion Chemical Disinfectants on Clinically Derived Poly(Vinyl Siloxane) Impressions.

PURPOSE: To comparatively evaluate the antimicrobial efficacy of freshly prepared electrolyzed oxidizing water (EOW) with that of 2.4% glutaraldehyde (GA) and 1% sodium hypochlorite (SH) on clinically derived poly vinyl siloxane (PVS) impressions. MATERIALS AND METHODS: Four clinically derived PVS impressions each were obtained from 10 subjects. One impression from each subject was randomly kept as control (group I), without disinfection. The remaining three impressions were randomly disinfected by immersion in either 2.4% GA (group II), 1% SH (group III), or freshly prepared EOW (group IV). The samples were subjected to microbial culture individually on brain heart infusion (BHI) agar medium. The organisms isolated were confirmed by visual examination and gram staining. Mean colony forming units (CFU) were counted, log10 reduction obtained and compared. Data were statistically analyzed using one-way ANOVA, followed by multiple comparisons using Tukey-HSD post hoc tests (p < 0.05). RESULTS: Streptococci, Staphylococci, Pseudomonas, Candida, Proteus, Klebsiella, and E. coli were isolated from all impressions including the controls, except those disinfected by EOW. All three disinfectants showed significant reduction in CFU and log10 reduction values as compared to the controls. EOW showed significantly higher reduction in log10 values compared to GA and SH, whereas GA and SH showed similar reductions. EOW, GA, and SH showed kill rates of 100%, 99.60%, and 99.82%, respectively. CONCLUSION: EOW showed significant antimicrobial efficacy as evidenced by reduction in log10 values when used as an immersion disinfectant for PVS impressions when compared with the results obtained using GA and SH. These results need further investigation. CLINICAL IMPLICATIONS: EOW shows high antimicrobial efficacy when used as an immersion disinfectant as compared to GA and SH for clinically derived PVS impressions.

Influence of Surface Modifications of Acrylic Resin Teeth on Shear Bond Strength with Denture Base Resin-An Invitro Study.

BACKGROUND: Debonding of artificial teeth from the denture base is an important issue for edentulous patients rehabilitated with conventional or implant supported complete dentures. AIM: The purpose of this study was to evaluate shear bond strength between denture base resin and acrylic resin denture teeth subjected to three different surface modifications on the ridge lap area as compared to unmodified denture teeth. MATERIALS AND METHODS: Forty acrylic resin central incisor denture teeth were selected and randomly divided into four test groups. The teeth in each group were subjected to one of the three different surface modifications, namely, chemical treatment, sandblasting and placement of retentive grooves on the ridge lap area respectively, prior to packing of the denture base resin. The group with unmodified teeth served as control. Forty acrylic resin test blocks thus obtained were tested for shear bond strength between acrylic resin teeth and denture base resin in Universal Testing Machine. Data obtained was statistically analysed using one-way ANOVA and Student- Newman- Keul's test (p< 0.05). RESULTS: Analysis of shear bond strength revealed that retentive grooves on the ridge lap area showed highest bond strength values followed by sandblasting and both were statistically significant compared to the control and chemically treated groups. Unmodified surface of the resin teeth showed the least bond strength. CONCLUSION: Within the limitations of this invitro study the placement of retentive grooves or sandblasting of the ridge lap area showed highly significant improvement in shear bond strength compared to the unmodified surface. Chemical treatment did not result in any significant improvement in the shear bond strength compared to the unmodified surface.

Restoration of Atrophic Edentulous Maxilla of a Patient with Ectodermal Dysplasia Using Quadruple Zygomatic Implants: A Case Report.

Rehabilitation of patients with ectodermal dysplasia often presents clinical challenge due to hypodontia, anodontia, and severe atrophy of edentulous ridges. Zygomatic implant therapy can be used as a method of achieving osseointegration without bone grafting in such situations. This clinical report describes the dental rehabilitation of atrophic maxilla of a 26-year old female patient with a fixed prosthesis, immediately loaded on four zygomatic implants.