Composition Of Gastrointestinal Fluids Research Articles

Characterization of neonatal and infant enterostomy fluids

The composition of gastrointestinal (GI) fluids is crucial for the dissolution, solubilization, and absorption of orally administered drugs. Disease- or age-related changes in GI fluid composition could significantly affect the pharmacokinetics of oral drugs. However, limited studies have been conducted on the characteristics of GI fluids in neonates and infants due to practical and ethical challenges. The current study collected enterostomy fluids from 21 neonate and infant patients over an extended period of time and from different regions of the small intestine and colon. The fluids were characterized for pH, buffer capacity, osmolality, total protein, bile salts, phospholipids, cholesterol, and lipid digestion products. The study found a large variability in the fluid characteristics among the different patients, in line with the highly heterogeneous study population. Compared to adult intestinal fluids, the enterostomy fluids from neonates and infants had low bile salt concentrations, with an increasing trend as a function of age; no secondary bile salts were detected. In contrast, total protein and lipid concentrations were relatively high, even in the distal small intestine. These findings suggest marked differences in intestinal fluid composition between neonates and infants versus adults, which may affect the absorption of certain drugs.

In- vitro biorelevant media and time simulation probiotic proliferation methodology to determine prebiotic potentials of flaxseed powder

Dysbiosis is defined as disorganization of microflora homeostasis, leading to changes in metabolic activities and local distribution with major impacts on functional composition. Presently, gut microbiota modifications, with the objective to treat microbial dysbiosis, is well known treatment option preferred for conditions involving gut flora disturbances. It has been found that the most common approach to treat gut flora disturbance is to prescribe probiotic supplements. The objective of the present research was to develop simple methodology in order to determine the prebiotic potential of flaxseed powder using a novel in-vitro bio-relevant media and a time simulation proliferation approach for the marketed probiotic Bacillus coagulans SNZ 1969, (“Sporlac Sachets, Sanzyme Biologics Private Limited”). In addition to the desired result, the current study also yielded pertinent information on fermented flaxseed powder and helpful data regarding prescription guidelines for commercially available probiotic supplements. It has been observed that various factors like gastrointestinal pH, transit time, gastrointestinal fluid composition, presence of prebiotics, and fermentation play an important role in the proliferation and gastrointestinal colonization of orally ingested probiotics. The research findings justify the importance of synbiotic and postbiotics supplement approaches as the part of treatment and prescription requirements in gut flora microbial dysbiosis rather than probiotic supplements alone. Alternatively, patients could be guided for the concept that the consumption of prebiotic-containing foods have potential to enhance the ability of probiotics to restore the gut flora following a course of antibiotic therapy.

Understanding the Impact of Age-Related Changes in Pediatric GI Solubility by Multivariate Data Analysis.

The aim of this study was to understand drug solubilization as a function of age and identify drugs at risk of altered drug solubility in newborns and young infants in comparison to adults. Multivariate statistical analysis was used to understand drug solubilization as a function of drug’s physicochemical properties and the composition of gastrointestinal fluids. The solubility of seven poorly soluble compounds was assessed in adult and age-specific fasted and fed state biorelevant media. Partial least squares regression (PLS-R) was used to assess the influence of (i) drug physicochemical properties and (ii) age-related changes in simulated GI fluids, as well as (iii) their interactions, on the pediatrics-to-adult solubility ratio (Sp/Sa (%)). For five out of seven of the compounds investigated, Sp/Sa (%) values fell outside of the 80–125% limits in at least one of the pediatric media. Lipophilicity was responsible for driving drug solubility differences between adults and children in all the biorelevant media investigated, while drug ionization was most relevant in the fed gastric media, and the fasted/fed intestinal media. The concentration of bile salts and lecithin in the fasted and fed intestinal media was critical in influencing drug solubility, while food composition (i.e., cow’s milk formula vs. soy formula) was a critical parameter in the fed gastric state. Changes in GI fluid composition between younger pediatric patients and adults can significantly alter drug luminal solubility. The use of pediatric biorelevant media can be helpful to identify the risk of altered drug solubilization in younger patients during drug development.

Impact of gastrointestinal differences in veterinary species on the oral drug solubility, in vivo dissolution, and formulation of veterinary therapeutics

Many gaps exist in our understanding of species differences in gastrointestinal (GI) fluid composition and the associated impact of food intake and dietary composition on in vivo drug solubilization. This information gap can lead to uncertainties with regard to how best to formulate pharmaceuticals for veterinary use or the in vitro test conditions that will be most predictive of species-specific in vivo oral product performance. To address these challenges, this overview explores species-specific factors that can influence oral drug solubility and the formulation approaches that can be employed to overcome solubility-associated bioavailability difficulties. These discussions are framed around some of the basic principles associated with drug solubilization, reported species differences in GI fluid composition, types of oral dosage forms typically given for the various animal species, and the effect of prandial state in dogs and cats. This basic information is integrated into a question-and-answer section that addresses some of the formulation issues that can arise in the development of veterinary medicinals.

A canine biorelevant dissolution method for predicting in vivo performance of orally administered sustained release matrix tablets

Preclinical species are a crucial component of drug development, but critical differences in physiology and anatomy need to be taken into account when attempting to extrapolate to humans or between species. The same is true when trying to develop oral formulations for preclinical species, especially unconventional formulations, such as sustained release tablets. During the evaluation of such specialized dosage forms, dissolution can be a critical in vitro tool used to rank-order formulations and ultimately choose the desired release rate. Here, the development of a canine biorelevant dissolution method for the prediction of the in vivo performance of sustained release matrix tablets in beagle dogs is described. The method accounts for differences in physiology between humans and dogs such as gastrointestinal fluid composition, gastric emptying forces, and gastric residence time. The most critical dissolution method parameters were found to be the paddle speed used to simulate the gastric emptying forces as well as the time spent in simulated gastric fluid. The resulting differences in method conditions are further explored through in silico models of the hydrodynamic forces applied to a dosage form. Two case studies are reported showing that the method was able to obtain excellent in vitro–in vivo relationships (slopes ranging from 1.08–1.01) which are significantly (p < 0.01–0.05) improved compared to human biorelevant dissolution used to predict in vivo performance in humans (slopes ∼1.5–1.75). The quality of the method’s predictive ability allows for it to help drive the development of matrix sustained release formulations intended for preclinical studies.

Characterization of particulate drug delivery systems for oral delivery of Peptide and protein drugs.

Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS). The aim of this review is to summarize the existing knowledge about oral delivery of peptide/protein drugs and to provide an overview of formulationand characterization strategies. For a better understanding of the challenges in oral delivery of peptide/protein drugs, the composition of GI fluids and the digestion processes of different kinds of excipients in the GI tract are summarized. Additionally, the paper provides an overview of recent studies on characterization of solid drug carriers for peptide/protein drugs, drug distribution in particles, drug release and stability in simulated GI fluids, as well as the absorption of peptide/protein drugs in cell-based models. The use of biorelevant media when applicable can increase the knowledge about the quality of DDS for oral protein delivery. Hopefully, the knowledge provided in this review will aid the establishment of improved biorelevant models capable of forecasting the performance of particulate DDS for oral peptide/protein delivery.

Different Dissolution Media Lead to Different Crystal Structures of Talinolol with Impact on Its Dissolution and Solubility

During the performance of dissolution tests with immediate and controlled-release talinolol tablets it was detected that the type of the buffer used as dissolution medium had a strong influence on the solubility and the dissolution behavior of the drug. It was proven that talinolol appeared in different crystal structures with strongly differing solubilities when pure water, acetate, or phosphate buffers were employed as dissolution media. The resulting crystal structures were characterized by means of light microscopy, differential scanning calorimetry, and X-ray powder diffraction. All methods were adjuvant to detect changes in talinolol crystal structures. The different solubility and dissolution properties of the talinolol salts or modifications may be viewed as a source for its incomplete and variable bioavailability. Furthermore, the food effect, described in the literature, that leads to a decrease in talinolol absorption, could be due to changes in the composition of gastrointestinal fluids leading to different talinolol crystal structures. Furthermore, it was detected that the addition of sodium chloride increases talinolol solubility and accelerates its dissolution from controlled-release tablets at concentrations between 0% and 1.25%, while an addition of sodium dodecylsulfate (SDS) as surfactant only had a solubility-improving effect at concentrations >0.75%. At lower concentrations SDS decreased the solubility of talinolol and notably decelerated its release from controlled-release tablets.