Crystal Structure, Solubility, and Pharmacokinetic Study on a Hesperetin Cocrystal with Piperine as Coformer

Hesperetin (HES) is a key biological active ingredient in citrus peels, and is one of the natural flavonoids that attract the attention of researchers due to its numerous therapeutic bioactivities that have been identified in vitro. As a bioenhancer, piperine (PIP) can effectively improve the absorption of insoluble drugs in vivo. In the present study, a cocrystal of HES and PIP was successfully obtained through solution crystallization. The single-crystal structure was illustrated and comprehensive characterization of the cocrystal was conducted. The cocrystal was formed by two drug molecules at a molar ratio of 1:1, which contained O–H–O hydrogen bonds between the carbonyl and ether oxygen of PIP and the phenolic hydroxyl group of HES. In addition, a solubility experiment was performed on powder cocrystal in simulated gastrointestinal fluid, and the result revealed that the cocrystal improves the dissolution behavior of HES compared with that of the pure substance. Furthermore, HES’s bioavailability in the cocrystal was six times higher than that of pristine drugs. These results may provide an efficient oral formulation for HES.

Case Report: Newborns With Pseudohypoaldosteronism Secondary to Excessive Gastrointestinal Losses Through High Output Stoma

Life-threatening electrolyte imbalance is not uncommon in preemies. Differential diagnosis is important for immediate treatment. The syndrome of pseudohypoaldosteronism (PHA) is characterized by increased aldosterone secretion associated with clinical signs of hypoaldosteronism reflecting mineralocorticoid resistance. There are type I, type II, and secondary type of PHA. Most secondary PHA reported in the pediatric population result from urinary infection and obstructive uropathy and extremely rarely from gastrointestinal fluid loss. Seven preemies accepted jejunostomy or ileostomy, and they suffered from high output stoma. Electrolyte imbalance with bodyweight loss or cardiac event was noted. We found a high level of aldosterone and renin and diagnosed them with secondary PHA due to excessive gastrointestinal losses. After stomal reversal, aldosterone and renin level became normalized, and electrolyte was corrected. This study reports the finding of secondary pseudohyperaldosteronism (hyponatremia, hyperkalemia, and metabolic acidosis) in a series of cases with intestinal resection and ostomy of different causes. Early stomal reversal was recommended.

Characterization of Cationic Modified Short Linear Glucan and Fabrication of Complex Nanoparticles with Low and High Methoxy Pectin

In this study, we chemically modified the short linear glucan (SLG) using the 3-chloro-2-hydroxypropyl trimethylammonium chloride to introduce a positive surface charge via cationization (CSLG). We then prepared CSLG-based binary nanocomplex particles through electrostatic interactions with low and high methoxyl pectin. The two new types of binary nanocomplex were comprehensively characterized. It was found that the nanocomplex particles showed a spherical shape with the particle size of < 700 nm, smooth surface, homogeneous distribution, and negative surface charge. Fourier transform infrared spectroscopy (FTIR) revealed that the driving forces to form nanocomplex were primarily electrostatic interactions and hydrogen bonding. In addition, increasing the CSLG concentration in the nanocomplex significantly enhanced both thermal stability and digestive stability. By comparing the two complex nanoparticles, the HMP-CSLG has a larger particle size and better stability under the GI condition due to the high content of the methoxy group. Additionally, the HMP-CSLG nanoparticle has a higher encapsulation efficiency and slower release rate under simulated gastrointestinal fluid for tangeretin compared with the LMP-CSLG. These results provide new insights into designing the CSLG-based nanocomplex as a potential oral delivery system for nutraceuticals or active ingredients.

Influence of osmolality on gastrointestinal fluid volume and drug absorption: potential impact on oral salt supplementation

Background The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is the most frequent cause of hyponatremia in patients with cerebrovascular disease, and is often treated with oral salt tablets. However, we have shown that osmolality-dependent variations in gastrointestinal (GI) fluid volume can alter the concentration of a poorly permeable drug in the GI tract, potentially affecting its absorption. Here, we examined the effect of ingestion of hyperosmotic solution (10% NaCl) on drug concentration and absorption in the GI tract. Methods The effects of osmolality on luminal fluid volume and drug absorption in rat intestine (jejunum, ileum and colon) were examined by means of an in situ closed loop method using fluorescein isothiocyanate-dextran 4000 (FD-4) and atenolol. In vivo absorption in rats was determined by measuring the plasma concentration after oral administration of the test compounds dissolved in purified water or hyperosmotic solution (10% NaCl). Results Administration of hyperosmotic solution directly into the GI tract significantly increased the GI fluid volume, owing to secretion of water into the lumen. After administration in hyperosmotic solution, the luminal concentration of non-permeable FD-4 was significantly lower than the initial dosing concentration, whereas after administration in purified water, the luminal concentration exceeded the initial concentration. The fraction absorbed of atenolol was markedly lower after administration in hyperosmotic solution than after administration in purified water. An in vivo pharmacokinetic study in rats was consistent with these findings. Conclusions Administration of hyperosmotic NaCl solution increased GI fluid volume and reduced the plasma level of orally administered atenolol. This may imply that oral salt tablets used to treat hyponatremia in SIADH patients could decrease the intestinal absorption of concomitantly administered drugs, resulting in lower plasma exposure.

Microencapsulation of Curcumin in Crosslinked Jelly Fig Pectin Using Vacuum Spray Drying Technique for Effective Drug Delivery

Microencapsulation of curcumin in jelly fig pectin was performed by the vacuum spray drying (VSD) technique. The VSD was advanced with a low inlet temperature of 80–90 °C and low pressure of 0.01 mPa. By the in situ cross-linking with multivalent calcium ions, jelly fig pectin produced stable curcumin encapsulated microparticles. The physiochemical characteristics of microparticles were thoroughly investigated. The results revealed that 0.75 w/w% of jelly fig pectin and inlet temperature of 90 °C could be feasible for obtaining curcumin microparticles. The VSD technique showed the best encapsulation efficiency and yield and loading efficiency was up to 91.56 ± 0.80%, 70.02 ± 1.96%, and 5.45 ± 0.14%, respectively. The curcumin was readily released into simulated gastrointestinal fluid with 95.34 ± 0.78% cumulative release in 24 h. The antioxidant activity was stable after being stored for six months and stored as a solution for seven days at room temperature before analysis. Hence, the VSD technique could be applicable for the microencapsulation of bioactive compounds such as curcumin to protect and use in the food/pharmaceutical industry.

Effects of 2′-Fucosyllactose-Based Encapsulation on Probiotic Properties in Streptococcus thermophilus

Streptococcus thermophilus is widely used in dairy fermentation as a starter culture for yogurt and cheese production. Many strains are endowed with potential probiotic properties; however, since they might not survive in adequate amounts after transit through the human gastrointestinal tract, it is advisable to improve cell survivability during this passage. The present study evaluates the use of 2′-fucosyllactose, a prebiotic molecule from human milk, compared with other known molecules, such as gelatin and inulin, to form alginate-based microcapsules to fulfill these requirements. Such microcapsules, obtained by the extrusion technique, were evaluated in terms of encapsulation efficiency, storage stability, gastrointestinal condition resistance, and cell release kinetics. Results reveal that microcapsules made using 2′-fucosyllactose and those with inulin resulted in the most efficient structure to protect S. thermophilus strain TH982 under simulated gastrointestinal conditions (less than 0.45 log CFU/g decrease for both agents). In addition, a prompt and abundant release of encapsulated cells was detected after only 30 min from microcapsules made with sodium alginate plus 2′-fucosyllactose in simulated gastrointestinal fluid (more than 90% of the cells). These encouraging results represent the first report on the effects of 2′-fucosyllactose used as a co-encapsulating agent.

Do the etiology of hyponatremia and serum sodium levels affect the length of hospital stay in geriatric patients with hyponatremia?

Introduction: Hyponatremia can lead to prolonged hospital stay, increased morbidity, and mortality rates in geriatric patients. The aim of this study was to evaluate the effects of hyponatremia etiology and serum sodium (Na) levels on hospitalization time in geriatric patients hospitalized due to hyponatremia. Method: The demographic characteristics, laboratory data, etiology of hyponatremia, and length of hospital stay were retrospectively recorded for 132 patients over 65 years of age who were hospitalized for hyponatremia. Findings: Of the 132 patients, 90 were female (68.2%) and 42 were male (31.8%). The serum Na levels of 66 (50%) patients were <120 mEq/L, of 64 (48.5%) patients were 120-129 mEq/L, and of 2 (1.5%) patients were >130 mEq/L. One hundred nine (82.6%) patients had hypoosmolar, 14 (10.6%) patients had isoosmolar, and 9 (6.8%) patients had hyperosmolar hyponatremia, and 19.7% of the patients were hypovolemic, 37.9% were euvolemic, and 42.4% were hypervolemic. Hyponatremia etiology was congestive heart failure in 38 (28.8%) patients, syndrome of inappropriate antidiuretic hormone in 29 (22.0%) patients, gastrointestinal fluid loss in 24 (18.2%) patients, renal pathologies in 20 (15.2%) patients, presence of drugs in 20 (15.2%) patients, and hypocortisolemia in 1 (0.8%) patient. The mean length of hospital stay of the patients was 5 (1-60) days. There was no statistically significant difference between the lengths of hospital stay in terms of hyponatremia etiologies and serum Na levels (p=0.861 and p=0.076). It was observed that the lengths of stay of patients who developed hyponatremia during their hospitalization in different clinics were longer than those of patients who presented to the emergency department (p<0.001). Conclusion: In this study it was determined that the length of hospital stay did not change with the etiology of hyponatremia and serum Na level at the time of admission, but patients who developed hyponatremia during their hospitalization had longer hospitalization time.

Amino Acids as the Potential Co-Former for Co-Crystal Development: A Review

Co-crystals are one of the most popular ways to modify the physicochemical properties of active pharmaceutical ingredients (API) without changing pharmacological activity through non-covalent interactions with one or more co-formers. A “green method” has recently prompted many researchers to develop solvent-free techniques or minimize solvents for arranging the eco-friendlier process of co-crystallization. Researchers have also been looking for less-risk co-formers that produce the desired API’s physicochemical properties. This review purposed to collect the report studies of amino acids as the safe co-former and explored their advantages. Structurally, amino acids are promising co-former candidates as they have functional groups that can form hydrogen bonds and increase stability through zwitterionic moieties, which support strong interactions. The co-crystals and deep eutectic solvent yielded from this natural compound have been proven to improve pharmaceutical performance. For example, l-glutamine could reduce the side effects of mesalamine through an acid-base stabilizing effect in the gastrointestinal fluid. In addition, some amino acids, especially l-proline, enhances API’s solubility and absorption in its natural deep eutectic solvent and co-crystals systems. Moreover, some ionic co-crystals of amino acids have also been designed to increase chiral resolution. Therefore, amino acids are safe potential co-formers, which are suitable for improving the physicochemical properties of API and prospective to be developed further in the dosage formula and solid-state syntheses.

Controlled drug release of levofloxacin from poly (acrylamide) hydrogel

Hydrogels are 3D polymer networks capable to absorb and release water or biological fluids. They are stimuli-responsive materials, which can show rapid volume changes with response to small changes in environmental parameters such as ionic strength, pH, and temperature. In this work, we performed a synthesis of Poly(acrylamide) hydrogel and tested for controlled release of levofloxacin hemihydrate as a model drug. We used sodium metabisulfite and potassium persulphate as free radical initiators to prepare hydrogel with methylenebisacrylamide as a crosslinker. Characterization of hydrogel was performed by TGA, SEM, and FT-IR. Swelling study and drug release were performed at pH 1.2 and 7.4 solutions, identical to the gastrointestinal fluid at 37°C (human body temperature) to examine possible site-specific drug delivery. UV-Visible spectrophotometer was used to measure the concentration of drug release. Results exhibited the pH and temperature-dependent drug release. The amount of drug release was found to be 17% and 99% in acidic and alkaline pH of 1.2 and 7.4, respectively, after 6 hours.