In Vitro Evaluation of Eslicarbazepine Delivery via Enteral Feeding Tubes

Purpose: The feasibility of preparing an eslicarbazepine acetate suspension using Aptiom tablets for administration via enteral feeding tubes was evaluated. Methods: Eslicarbazepine acetate suspension (40 mg/mL) was prepared using Aptiom tablets after optimizing the tablet crushing methods and the vehicle composition. A stability-indicating high-performance liquid chromatography (HPLC) method was developed to monitor the eslicarbazepine stability in the prepared suspension. Three enteric feeding tubes of various composition and dimensions were evaluated for the delivery of the suspensions. The suspension was evaluated for the physical and chemical stability for 48 hours. Results: The reproducibility and consistency of particle size reduction was found to be best with standard mortar/pestle. The viscosity analysis and physical stability studies showed that ORA-Plus:water (50:50 v/v) was optimal for suspending ability and flowability of suspension through the tubes. The developed HPLC method was found to be stability indicating and suitable for the assay of eslicarbazepine acetate in the prepared suspension. The eslicarbazepine concentrations in separately prepared suspensions were within acceptable range (±3%), indicating accuracy and reproducibility of the procedure. The eslicarbazepine concentrations in suspensions before and after delivery through the enteric feeding tubes were within acceptable range (±4%), indicating absence of any physical/chemical interactions of eslicarbazepine with the tubes and a successful delivery of eslicarbazepine dosage via enteric feeding tubes. The stability study results showed that eslicarbazepine concentration in the suspension remained unchanged when stored at room temperature for 48 hours. Conclusion: The study presents a convenient procedure for the preparation of a stable suspension of eslicarbazepine acetate (40 mg/mL) using Aptiom tablets, for administration via enteral feeding tubes

An Exploratory Study of Suboxone (Buprenorphine/ Naloxone) Film Splitting: Cutting Methods, Content Uniformity, and Stability

Suboxone films are U.S. Food and Drug Administration approved to treat opioid dependence. While the package insert states that films should not be cut, physicians often prescribe film fractions for treatment and tapering. There is no data to support this practice, and this study was initiated to evaluate cutting methods, content uniformity, and stability of split films. Suboxone 8-mg buprenorphine/2-mg naloxone films were split using four methods: 1) ruler/razor cut, 2) scissor cut, 3) fold/rip, and 4) fold/scissor cut. United States Pharmacopeia Chapter \u3c905\u3e was used to evaluate the weight variation and content uniformity of split films. The stability of split films stored in polybags was evaluated over 7 days. A stability-indicating high-performance liquid chromatography method was used for content uniformity and stability evaluation. The weight variation results were acceptable for the half films from all four cutting methods, but this was not true for the quarter films. The method of ruler/razor cut was determined most favorable and used for the content uniformity test. Based on the high-performance liquid chromatography results, the half films from the ruler/razor cut method met the passing criteria of United States Pharmacopeia Chapter \u3c905\u3e with acceptance values of 9.8 to 10.4 for buprenorphine and 8.4 to 11.5 for naloxone (≤15 is considered passing). The stability results indicated that both actives retained \u3e97.7% of initial strength. Four cutting methods were found to be acceptable for splitting Suboxone films into half but not quarter fractions. The half films from the ruler/razor cut method also passed United States Pharmacopeia Chapter \u3c905\u3e content uniformity test. Both actives remained stable for 7 days when the half films were stored in polybags at room temperature

Physical and Chemical Stability of Dexamethasone Sodium Phosphate in Intravenous Admixtures Used to Prevent Chemotherapy-Induced Nausea and Vomiting

Purpose: Dilute intravenous (IV) admixtures of dexamethasone sodium phosphate (DSP) are becoming increasingly used in antiemetic regimens to prevent chemotherapy-induced nausea and vomiting (CINV). Based on its chemical structure and previous studies, DSP is known to be susceptible to hydrolysis and oxidation under certain conditions. There are limited data to directly support the selection of IV diluents, storage conditions, and beyond-use dates for the dilute IV solutions of DSP used in the antiemetic regimens. This study was designed to investigate these parameters. Methods: A stability-indicating high-performance liquid chromatography (HPLC) method was first developed for the analysis of DSP. Commercially available 100 mg/10 mL DSP injection vials were used to prepare the IV admixtures of DSP in 0.9% sodium chloride injection or 5% dextrose injection. The final DSP concentrations were 0.08 or 0.4 mg/mL, which bracketed the range commonly used in antiemetic regimens. These admixtures were packaged in 50-mL polyvinylchloride (PVC) bags and stored at room temperature or under refrigeration for 14 days. Samples from each IV bag underwent visual, pH, and HPLC assessments on days 0, 1, 3, 7, and 14. Results: Immediately after preparation, the IV admixtures of DSP appeared clear, colorless, and free of particulate matters. The initial pH values were 6.4 to 6.8 and 7.0 to 7.8 for samples in 0.9% sodium chloride and 5% dextrose, respectively. The initial DSP concentrations of all samples were within 96% to 100% of the expected values. Over the 14 days of storage at room temperature or refrigeration, no significant change was observed for the visual appearance of any IV bags. The pH of all samples remained within one pH unit from the initial values. The HPLC results confirmed that all samples retained 94% to 100% of original drug concentrations and that no significant degradation products were observed. Conclusions: Intravenous admixtures of DSP at 0.08 to 0.4 mg/mL are compatible with 0.9% sodium chloride and 5% dextrose in PVC bags. These admixtures are also chemically and physically stable when stored at room temperature or under refrigeration for up to 14 days

An integrative approach to ancient agricultural terraces and forms of dependency: the case of Cutamalla in the prehispanic Andes

This paper presents an integrative and interdisciplinary approach to the study of ancient agricultural terraces and food production systems. Our approach consists of (1) a resource dependency theoretical framework and (2) the application of a variety of archaeological and geoscientific methods, including archaeological and geomorphological surveys, archaeological excavations, drone surveys, mapping based on satellite imagery and high-resolution digital elevation models (DEMs), geographic information system (GIS) applications, soil testing, phytolith analysis, radiocarbon dating, and calculations of food supply capacity and labor requirements. We apply these to the prehispanic site of Cutamalla (3,300 m asl) in the southern Peruvian Andes, which serves as an ideal and pioneering case study. Previous research has focused primarily on the settlement of Cutamalla, particularly through large-scale archaeological excavations, but less attention has been paid to the extensive farming terraces surrounding the settlement and the close relationship between agricultural and settlement activities. By analyzing both the terrace and settlement levels, we take a new perspective and introduce the term agricultural terrace-settlement system for such complexes. Our results show that the residential occupation of Cutamalla and the use of the surrounding farming terraces coincided: the agricultural terrace-settlement system was intensively used for a relatively short period of about 200 years (~250–40 BCE) during the Formative Late Paracas and transitional Initial Nasca periods, long before the famous Inka terrace agricultural systems. There is no evidence of reoccupation of the site and subsequent reuse of the agricultural system. Our data also document the large extent of agricultural terraces around Cutamalla (221 ha) and that maize was likely a major crop grown there. Finally, we place these findings in their broader socio-economic and ecological context. Cutamalla was an important regional center and economic hub during a very dynamic period characterized by significant population growth and increased violence. Not only a more humid climate, but probably also forced collective labor were cornerstones of substantial agricultural production in Cutamalla and the region

Reconstructing the Deep Population History of Central and South America

We report genome-wide ancient DNA from 49 individuals forming four parallel time transects in Belize, Brazil, the Central Andes, and the Southern Cone, each dating to at least 9,000 years ago. The common ancestral population radiated rapidly from just one of the two early branches that contributed to Native Americans today. We document two previously unappreciated streams of gene flow between North and South America. One affected the Central Andes by 4,200 years ago, while the other explains an affinity between the oldest North American genome associated with the Clovis culture and the oldest Central and South Americans from Chile, Brazil, and Belize. However, this was not the primary source for later South Americans, as the other ancient individuals derive from lineages without specific affinity to the Clovis-associated genome, suggesting a population replacement that began at least 9,000 years ago and was followed by substantial population continuity in multiple regions

In Vitro Evaluation of Eslicarbazepine Delivery via Enteral Feeding Tubes

Purpose: The feasibility of preparing an eslicarbazepine acetate suspension using Aptiom tablets for administration via enteral feeding tubes was evaluated. Methods: Eslicarbazepine acetate suspension (40 mg/mL) was prepared using Aptiom tablets after optimizing the tablet crushing methods and the vehicle composition. A stability-indicating high-performance liquid chromatography (HPLC) method was developed to monitor the eslicarbazepine stability in the prepared suspension. Three enteric feeding tubes of various composition and dimensions were evaluated for the delivery of the suspensions. The suspension was evaluated for the physical and chemical stability for 48 hours. Results: The reproducibility and consistency of particle size reduction was found to be best with standard mortar/pestle. The viscosity analysis and physical stability studies showed that ORA-Plus:water (50:50 v/v) was optimal for suspending ability and flowability of suspension through the tubes. The developed HPLC method was found to be stability indicating and suitable for the assay of eslicarbazepine acetate in the prepared suspension. The eslicarbazepine concentrations in separately prepared suspensions were within acceptable range (±3%), indicating accuracy and reproducibility of the procedure. The eslicarbazepine concentrations in suspensions before and after delivery through the enteric feeding tubes were within acceptable range (±4%), indicating absence of any physical/chemical interactions of eslicarbazepine with the tubes and a successful delivery of eslicarbazepine dosage via enteric feeding tubes. The stability study results showed that eslicarbazepine concentration in the suspension remained unchanged when stored at room temperature for 48 hours. Conclusion: The study presents a convenient procedure for the preparation of a stable suspension of eslicarbazepine acetate (40 mg/mL) using Aptiom tablets, for administration via enteral feeding tubes

Physical and Chemical Stability of Dexamethasone Sodium Phosphate in Intravenous Admixtures Used to Prevent Chemotherapy-Induced Nausea and Vomiting

Purpose: Dilute intravenous (IV) admixtures of dexamethasone sodium phosphate (DSP) are becoming increasingly used in antiemetic regimens to prevent chemotherapy-induced nausea and vomiting (CINV). Based on its chemical structure and previous studies, DSP is known to be susceptible to hydrolysis and oxidation under certain conditions. There are limited data to directly support the selection of IV diluents, storage conditions, and beyond-use dates for the dilute IV solutions of DSP used in the antiemetic regimens. This study was designed to investigate these parameters. Methods: A stability-indicating high-performance liquid chromatography (HPLC) method was first developed for the analysis of DSP. Commercially available 100 mg/10 mL DSP injection vials were used to prepare the IV admixtures of DSP in 0.9% sodium chloride injection or 5% dextrose injection. The final DSP concentrations were 0.08 or 0.4 mg/mL, which bracketed the range commonly used in antiemetic regimens. These admixtures were packaged in 50-mL polyvinylchloride (PVC) bags and stored at room temperature or under refrigeration for 14 days. Samples from each IV bag underwent visual, pH, and HPLC assessments on days 0, 1, 3, 7, and 14. Results: Immediately after preparation, the IV admixtures of DSP appeared clear, colorless, and free of particulate matters. The initial pH values were 6.4 to 6.8 and 7.0 to 7.8 for samples in 0.9% sodium chloride and 5% dextrose, respectively. The initial DSP concentrations of all samples were within 96% to 100% of the expected values. Over the 14 days of storage at room temperature or refrigeration, no significant change was observed for the visual appearance of any IV bags. The pH of all samples remained within one pH unit from the initial values. The HPLC results confirmed that all samples retained 94% to 100% of original drug concentrations and that no significant degradation products were observed. Conclusions: Intravenous admixtures of DSP at 0.08 to 0.4 mg/mL are compatible with 0.9% sodium chloride and 5% dextrose in PVC bags. These admixtures are also chemically and physically stable when stored at room temperature or under refrigeration for up to 14 days

Stability of Dexamethasone Sodium Phosphate in Intravenous Admixtures

Objective: Diluted IV solutions of dexamethasone sodium phosphate (DSP) are often used in prophylactic treatment of chemotherapy-induced nausea and vomiting. However, there is limited data to support the selection of diluents, storage conditions, and beyond-use dates. This study was designed to investigate these parameters. Methods: DSP injection 100 mg/10 mL vials were used to prepare the IV admixtures in two diluents and at two drug concentrations (0.08 or 0.4 mg/mL). The admixtures were packaged in PVC bags and stored at room temperature or under refrigeration for up to 14 days. On day-0, 1, 3, 7, and 14, each IV bag was inspected visually, and a sample was withdrawn for pH and HPLC analysis. Results: The freshly prepared admixtures of DSP appeared clear, colorless, and free of particulates. The initial pH values were 6.4-6.8 and 7.0-7.8 for bags in 0.9% sodium chloride and 5% dextrose, respectively. The initial DSP concentrations of all samples were within 96 – 100% of the expected values. Over the 14 days of storage at room temperature or refrigeration, no significant change was observed for the visual appearance of any IV bags. The pH of all samples remained within one pH unit from the initial values. The HPLC results confirmed that all samples retained 94 – 100% of original drug concentrations. Implications: IV admixtures of 0.08 - 0.4 mg/mL DSP are compatible with 0.9% sodium chloride and 5% dextrose in PVC bags. These admixtures are also chemically and physically stable for up to 14 days when stored at room temperature or under refrigeration

Stability of Dexamethasone Sodium Phosphate in Intravenous Admixtures

Objective: Diluted IV solutions of dexamethasone sodium phosphate (DSP) are often used in prophylactic treatment of chemotherapy-induced nausea and vomiting. However, there is limited data to support the selection of diluents, storage conditions, and beyond-use dates. This study was designed to investigate these parameters. Methods: DSP injection 100 mg/10 mL vials were used to prepare the IV admixtures in two diluents and at two drug concentrations (0.08 or 0.4 mg/mL). The admixtures were packaged in PVC bags and stored at room temperature or under refrigeration for up to 14 days. On day-0, 1, 3, 7, and 14, each IV bag was inspected visually, and a sample was withdrawn for pH and HPLC analysis. Results: The freshly prepared admixtures of DSP appeared clear, colorless, and free of particulates. The initial pH values were 6.4-6.8 and 7.0-7.8 for bags in 0.9% sodium chloride and 5% dextrose, respectively. The initial DSP concentrations of all samples were within 96 – 100% of the expected values. Over the 14 days of storage at room temperature or refrigeration, no significant change was observed for the visual appearance of any IV bags. The pH of all samples remained within one pH unit from the initial values. The HPLC results confirmed that all samples retained 94 – 100% of original drug concentrations. Implications: IV admixtures of 0.08 - 0.4 mg/mL DSP are compatible with 0.9% sodium chloride and 5% dextrose in PVC bags. These admixtures are also chemically and physically stable for up to 14 days when stored at room temperature or under refrigeration