Peptide Drug Delivery: Injection Devices, Oral Systems & Formulations

Subcutaneous injection remains the most common route for approved peptide medicines.

To overcome patient resistance to needle injections, modern pharmaceutical engineering has transitioned from traditional syringes to advanced delivery platforms:

• Multi-Dose Disposable Pens: Pre-filled pen injectors (such as the Ozempic and Victoza pens) featuring dial-a-dose mechanisms, disposable 32-gauge ultra-fine needles (4 mm length), and automatic dose-confirmation clicks.
• Single-Dose Auto-Injectors: Fully automated, push-button or contact-activated devices (such as the Wegovy and Mounjaro autoinjectors) where the needle remains completely shielded before and after injection, protecting against accidental needle-sticks.
• On-Body Wearable Delivery Systems: Adherent wearable pumps that administer high-volume peptide formulations slowly over several minutes.

Handheld autoinjectors are also being developed for larger single-dose volumes. A systematic review of 31 studies of subcutaneous delivery above 1.0 mL concluded that the literature supports the feasibility of delivering larger single subcutaneous volumes, while injection tolerability, suitability for self-administration and pharmacokinetic equivalence remain key design questions [1].

Developing oral tablets for peptide drugs has long represented one of the most formidable challenges in pharmaceutical formulation [2]. Successful commercialization requires overcoming both enzymatic and physical barriers:

• pH-Dependent Enteric Coatings: Polymers (such as Eudragit) that remain insoluble in the acidic stomach (pH < 5.5) but dissolve rapidly upon reaching the neutral small intestine (pH 6.5–7.5).
• Chemical Permeation Enhancers (CPEs): Surfactants and fatty acid derivatives, such as sodium caprate (C10) and SNAC, that transiently perturb lipid packing in mucosal cell membranes or loosen tight junction claudin proteins, creating a brief window for transcellular or paracellular peptide absorption [2].

The human lung is an attractive non-invasive delivery portal because of its large, thin absorptive surface in the deep alveoli.

In 2014, the FDA approved Afrezza, an inhalable rapid-acting human insulin dry powder. Afrezza uses Technosphere microparticle technology (insulin carried on fumaryl diketopiperazine, FDKP, microparticles). Technosphere insulin is quickly absorbed in the alveoli, with a time to maximum plasma concentration of approximately 14 minutes, and its effect profile more closely matches post-meal insulin concentrations seen in people without diabetes than conventional prandial insulins [3].

For chronic conditions requiring continuous receptor suppression (such as prostate cancer, acromegaly, and endometriosis), daily or weekly injections are inefficient. Chemists utilize poly(lactic-co-glycolic acid) (PLGA) microspheres [4].

Peptide molecules are microencapsulated into biodegradable PLGA polymer spheres. Following deep intramuscular injection (as in Sandostatin LAR [octreotide] or Lupron Depot [leuprolide]), the polymer slowly degrades via non-enzymatic ester hydrolysis into natural lactic acid and glycolic acid, releasing a sustained, continuous trickle of therapeutic peptide over 1 to 6 months [4].

An emerging frontier is transdermal microneedle arrays [5]. These patches contain arrays of microscopic needles measuring hundreds of microns in length.

When applied to the skin, microneedles pierce the outermost dead stratum corneum barrier to access the viable epidermis and upper dermis. Microneedle patches are designed to deliver drugs and vaccines into the skin in a painless, easy-to-use manner. A small number of human clinical trials suggest they can be used safely and with strong patient acceptance, but more advanced clinical trials and commercial-scale manufacturing are still needed [5].