Physiologically Based Biopharmaceutics Modeling (PBBM): Best Practices for Drug Product Quality, Regulatory and Industry Perspectives: 2023 Workshop Summary Report.

Physiologically based biopharmaceutics modeling (PBBM) is used to elevate drug product quality by providing a more accurate and holistic understanding of how drugs interact with the human body. These models are based on the integration of physiological, pharmacological, and pharmaceutical data to simulate and predict drug behavior in vivo. Effective utilization of PBBM requires a consistent approach to model development, verification, validation, and application. Currently, only one country has a draft guidance document for PBBM, whereas other major regulatory authorities have had limited experience with the review of PBBM. To address this gap, industry submitted confidential PBBM case studies to be reviewed by the regulatory agencies; software companies committed to training. PBBM cases were independently and collaboratively discussed by regulators, and academic colleagues participated in some of the discussions. Successful bioequivalence "safe space" industry case examples are also presented. Overall, six regulatory agencies were involved in the case study exercises, including ANVISA, FDA, Health Canada, MHRA, PMDA, and EMA (experts from Belgium, Germany, Norway, Portugal, Spain, and Sweden), and we believe this is the first time such a collaboration has taken place. The outcomes were presented at this workshop, together with a participant survey on the utility and experience with PBBM submissions, to discuss the best scientific practices for developing, validating, and applying PBBMs. The PBBM case studies enabled industry to receive constructive feedback from global regulators and highlighted clear direction for future PBBM submissions for regulatory consideration.

Assessment of Bone Quality Using Radiogrammetric Parameters of Proximal Humerus in India: Defining the Osteoporotic Fracture Risk Limit Value and its Reliability.

BACKGROUND: World health organization (WHO) has defined osteoporosis clinically on the basis of bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry (DXA) scan and the presence of fractures. This facility is expensive and not readily available in majority of the centers in India. The authors have attempted to study defined measurements on radiographs (radiogrammetric parameters) to diagnose osteoporosis in Indian population. PATIENTS AND METHODS: We prospectively studied 200 proximal humerus radiographs for measuring radiogrammetric parameters and divided into Group A and B (N = 100 in each group). Group A involved patients with age < 50 years and without any illness affecting bone quality. Group B involved patients with age > 50 years and sustained acute osteoporotic fractures of distal radius/ anterior wedge vertebral fracture/intertrochanteric fracture following trivial trauma. Three parameters (cortical thickness, cortical index and deltoid tuberosity index) were measured by 3 observers at 2 different occasions. RESULTS: The mean age of patients was 37.87 years and 58.38 years for group A and B, respectively. The 'cortical thickness' of the proximal humerus diaphysis had the mean value for Group A and B to be 0.4 ± 0.07 cm and 0.33 ± 0.06 cm respectively. The mean values for the 'cortical index' of proximal humerus came out to be 0.4 ± 0.07 for group A and 0.32 ± 0.06 for group B. The 'deltoid tuberosity index' measurements showed the mean values for group A and B were 1.81 ± 0.23 and 1.55 ± 0.16, respectively. Inter-observer reliability for single measures was excellent for deltoid tuberosity index (ICC 0.8077) and good for cortical thickness (ICC 0.7032) and cortical index (ICC 0.7357). Observer 1 had excellent intra-observer reliabilities for all the three parameters. Observer 2 and 3 had excellent reliability for deltoid tuberosity index and good intra-observer reliability for cortical thickness and cortical index. The cortical thickness had a cut off of ≤ 0.372 cm with a sensitivity of 86.02 and specificity of 82.12. The cortical index had a cut off of ≤ 0.378 with a sensitivity of 89.16 and specificity of 84.22. The deltoid tuberosity index had a cut off of ≤ 1.684 with a sensitivity of 96.61 and specificity of 84.08. CONCLUSION: The outcome of this study is likely to help in early diagnosis of osteoporosis at the community level in the absence of DXA scan as it identifies threshold values for radiogrammetric parameters which can be a predictor of the osteoporosis. The deltoid tuberosity index was found to be the most suitable of these parameters.

Bioavailability assessment of zinc enriched lactobacillus biomass in a human colon carcinoma cell line (Caco-2).

The present study utilizes lactobacilli strains having the potential to accumulate a significant amount of Zinc (Zn) in their biomass and ability to deliver the same mineral in a highly bioavailable form. A human origin Lactobacillus fermentum SR4 and Lactobacillus rhamnosus GG (LGG) were studied for their ability to accumulate Zn by growing them in the medium containing Zn salt. Further, Zn enriched cell lysates were prepared by Ultrasonication, as an organic Zn source. Various functional groups involved in bacterial Zn binding were identified by FT-IR spectroscopy and elemental Zn in bio-chelated cell lysate complex was confirmed by SEM and Energy Dispersive X-ray Spectrometry (EDX). Experimental data demonstrated a significantly higher (P < 0.05) bioavailability of Zn chelated by SR4 followed by LGG i.e., 57% and 48%, as compared to the commercially available inorganic (ZnSo4) and even organic (Zinc gluconate) forms tested which has 15.6% and 21.7% respectively.

In vivo assessment of iron bioavailability from fortified pearl millet based weaning food.

BACKGROUND: Iron is an essential micronutrient required for normal growth and development of the body. Infants are more vulnerable to develop iron-deficiency anaemia due to inadequate iron supply in early stages. The objective of the study was in vivo assessment of iron bioavailability from pearl millet based weaning food fortified with iron and vitamin A, and to investigate the role of vitamin A in iron absorption in animal models. RESULTS: Results revealed that anaemic group showed significantly (P < 0.05) higher bioavailability than that of normal rat models. Animals fed vitamin A supplemented pearl-millet diet exhibited comparable results with a sub-group provided commercially available weaning diet in both normal and anaemic groups, but significantly (P < 0.05) higher values for studied biological indices than that of a sub-group provided iron fortified pearl-millet or synthetic diet. When the anaemic rats were provided iron + vitamin A fortified diet, iron bioavailability increased and liver iron stores returned to the normal levels after 30 days, indicating a promoter role of vitamin A in intestinal iron absorption. CONCLUSIONS: Overall, bioavailability of electrolytic iron could be improved by supplementation of vitamin A, and this mixture can be considered as a useful fortificant for pearl millet based complementary foods fortification designed to prevent iron deficiency. © 2016 Society of Chemical Industry.

Assessment of stability of binary sweetener blend (aspartame x acesulfame-K) during storage in whey lemon beverage.

In the present study, artificial sweeteners-aspartame, acesulfame-K and binary sweetener blend of aspartame x acesulfame-K were assessed for stability during storage in whey lemon beverage. A solid phase extraction method using C18 cartridges was standardized for the isolation of aspartame, acesulfame-K and their degradation products in whey lemon beverage. HPLC analytical conditions were standardized over C18 column for simultaneous separation of multiple sweeteners and their degradation products in sample isolates. Storage studies revealed that increase in acidity and viscosity and decrease in pH and ascorbic acid content of artificially sweetened whey lemon beverage samples were similar to the changes occurring in control samples during storage. Analysis using HPLC showed that aspartame (added either singly or in a blend) and acesulfame-K (added in a blend) were stable in whey lemon beverage under refrigerated condition for 15 days.