Scalable Gastric Resident Systems for Veterinary Application

Abstract

Gastric resident dosage forms have been used successfully in farm animals for the delivery of a variety of drugs helping address the challenge of extended dosing. Despite these advances, there remains a significant challenge across the range of species with large variation in body size. To address this, we investigate a scalable gastric resident platform capable of prolonged retention. We investigate prototypes in dimensions consistent with administration and retention in the stomachs of two species (rabbit and pig). We investigate sustained gastric retention of our scalable dosage form platform, and in pigs show the capacity to modulate drug release kinetics of a model drug in veterinary practice, meloxicam, with our dosage form. The ability to achieve gastric residence and thereby enable sustained drug levels across different species may have a significant impact in the welfare of animals in both research, agricultural, zoological, and clinical practice settings.

Milk exosomes with enhanced mucus penetrability for oral delivery of siRNA

“…is significantly limited due to several biological barriers, which include the propensity for enzymatic and acidic degradation in the gastrointestinal (GI) tract and considerably limited permeation across the intestinal mucosal and epithelial cell layers. [4][5][6] Although permeation enhancers like caprates have shown some promise with a GLP-1 peptide drug approved for clinical use, the oral bioavailability of the drug from this formulation is only about 1%. 7 While particles such as liposomes can encapsulate and protect therapeutics against enzymatic degradation, the negatively charged, hydrophobic mucosal membrane lining the intestinal epithelium presents significant steric hindrance to the diffusive transport of such particulate systems.…”

A once-a-month oral contraceptive

“…The mechanical integrity of the materials used to make the arms of the gastric resident dosage forms was tested in SGF in vitro (24). Based on our previous experience, we decided to use Sorona 3015 G NC010 to make the arms.…”

“…Gastric retentive dosage forms were manufactured as described before (23,24) with minor changes. The arm casings of the dosage form were manufactured from Sorona 3015G NC010 using a microcompounder and an injection molder as described in the Supplementary Materials.…”

“…To address this issue, we have developed a gastric resident dosage form that can be placed in a gelatin capsule to enable oral administration. This dosage form, once ingested, expands and resides in the stomach for extended periods (23)(24)(25), providing drug release for 3 weeks with a hormone-free period, which would be associated with the recognized breakthrough bleeding that would also serve as a reminder for the next monthly dose. Using this dosage form, we have shown 1-to 2-week-long delivery of anti-infectious disease agents previously (23,25); however, month-long delivery of contraceptives has yet to be achieved.…”

Retentive drug delivery systems based on shape memory materials

“…Expansion‐dependent retention tools also underlie a number of cutting‐edge engineered devices, and related construction materials, aimed at gastric residence times beyond 24 h up to several weeks . In this respect, star‐shaped and spherical fenestrated structures, subject to in situ reversible expansion due to elastic unfolding, and a pufferfish‐like hydrogel system having high‐speed, high‐ratio, and durable water swelling have been described, for human and/or veterinary application . All of them would notably match the "Ultra‐long‐acting oral formulation" category of FDA's Emerging Technology Program, which has been launched by the agency to endorse adoption of innovative pharmaceutical design and manufacturing schemes entailing purposely set regulatory evaluation approaches .…”