Permeability Evaluation of Generic Drug

Drug molecules encounter a number of different membrane barriers in living systems, including gastrointestinal (GI) epithelial cells, capillary walls, hepatocyte membranes, glomeruli, restrictive organ barriers (e.g., blood-brain barrier), and target cell membranes. Permeability, which refers to the rate at which drug molecules pass through these biofilm barriers, is a critical factor affecting the bioavailability of orally administered drugs. Since compounds must pass through cell membranes to reach intracellular therapeutic targets, permeability is also important for cell-based bioassays during the drug discovery phase. Alfa Chemistry can accurately and efficiently evaluate the permeability of generic drugs, and further analyze the rate and extent of drug uptake into the body, as well as the bioavailability of the drug.

Figure 1. The transport mechanisms from the lumen across the intestinal epithelium, which determine the net permeability of a luminally dissolved drug molecule. ( Dahlgren D, et al. 2019)

Alfa Chemistry's Services

We offer a variety of models to predict the permeability of generic drugs in vitro and in vivo, helping you to analyze the intrinsic properties of the drug to give a more accurate evaluation of the generic drug.

In Vivo Intestinal Perfusion Modeling in Animals

In this method, the target intestinal segment is surgically removed from the body of the experimental animal by opening the abdominal cavity, and a catheter is inserted at both ends to instill the drug into the intestinal lumen at a certain flow rate, and then the effluent is collected at regular intervals, and the concentration of the drug is measured by analytical means.

We offer both in vivo unidirectional and closed-loop intestinal perfusion models, which have the advantage of relatively reducing the amount of enema fluid and drug used, are more suitable for low-permeability drugs.

Isolated Intestinal Capsule Model

If the anesthetics injected into the animal during the experiment affects the results of the generic drug, we will use an ex vivo model for you. We have successfully established the ex vivo model, the non-ex vivo model, and the Eus perfusion model, etc. These models can be used to study the absorption of drugs in different intestinal segments and drug-drug interactions.

Cell Model

Human colon cancer cell epithelial cells ( Caco-2) model:

Caco-2 cells are commonly used to determine the permeability of drugs, which is used to study the bidirectional drug transport, and to calculate the apparent permeability coefficient of drugs by examining the time, drug concentration, and other factors.

The advantage of Caco-2 cells is that they are homologous and can be used to distinguish the difference of different absorption routes in the intestinal lumen, determine the mode of drug absorption, and find out the pharmacokinetic parameters of drug absorption.

Canine renal cell (MDCK) model:

We provide the MDCK-MDR1 cell model, using liquid-liquid-mass spectrometry to determine the drug concentration and calculate the apparent permeability coefficient of drug permeation through the monolayer of cells. The advantage of the MDCK cell model is that the incubation time of MDCK cells is shorter than that of Caco-2 cells.

Parallel Artificial Membrane (PAMPA) Permeation Model

PAMPA is an artificial phospholipid used as a biofilm to mimic a drug barrier across membranes. We offer the PAMPA permeation model to determine the passive transmembrane permeation of generic drugs. It provides rapid information about the passive transport of drugs and is an excellent alternative to cellular models.

Characteristics of the PAMPA Model

The advantages of the PAMPA model are high throughput and low cost:

• Compared with animal enteral perfusion, PAMPA eliminates the need for animal feeding, shortens the experimental time, and improves experimental efficiency.
• Compared to the Caco-2 cell model, PAMPA eliminates the need for cell culture and accepts a wider pH range to better mimic the physiological environment. In addition, PAMPA can accept higher levels of dimethyl sulfoxide, resulting in better solubility of the samples, which is more conducive to later analysis.