Polymeric Nanoparticles for Enhancing the Oral Bioavailability of Poorly Soluble Antihypertensive Drugs: Formulation Design and Biopharmaceutical Evaluation

Hypertension needs lifelong treatment, and almost all of that treatment is given by mouth. Several widely prescribed antihypertensives, including dihydropyridine calcium channel blockers, carvedilol and the lipophilic sartan prodrugs, dissolve poorly in gastrointestinal fluids, so their oral bioavailability is low and often variable. Nanoparticle formulations are one way to deal with this. This review looks at the biopharmaceutical basis of the problem, the drugs that actually have solubility-limited absorption, and the main nanocarrier platforms: polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and self-nanoemulsifying systems, and drug nanocrystals. It then covers formulation materials, preparation methods, mechanisms of bioavailability enhancement, characterisation, and pharmacokinetic evaluation. Published studies on felodipine, carvedilol, candesartan cilexetil, olmesartan medoxomil and nifedipine are compared with our own laboratory work on PLGA nanoparticles of losartan potassium. That work produced a 186 nm, −28.6 mV batch with 86.7% encapsulation efficiency, which released 96.4% of the drug in 12 h compared with 71.6% for a conventional formulation. The evidence is strongest for faster dissolution and higher apparent solubility. Claims of greater permeation, lymphatic transport or avoidance of first-pass metabolism depend on the drug and the carrier, and are often inferred rather than measured. Gains in exposure have so far been shown mostly in rodents, and controlled human studies are rare. Losartan illustrates why classification comes before formulation: it is highly water-soluble, and its incomplete bioavailability comes from first-pass metabolism, not dissolution. We conclude that nanoparticle design for antihypertensives should start from biopharmaceutical data. Studies should also include proper comparators, biorelevant testing and pharmacokinetic endpoints, and should address safety, stability and scale-up early if clinical benefit is to be demonstrated. Keywords: Hypertension; Poorly soluble drugs; Polymeric nanoparticles; PLGA; Oral bioavailability; Biopharmaceutics Classification System; Lipid nanocarriers; Nanocrystals