Lipid-Based Drug Delivery Systems for Poorly Water-Soluble Drugs: A Review

Poor water solubility is still one of the toughest problems in drug development today. It really limits how effective a lot of new drugs can be. Around 40–70% of new chemical compounds just don’t dissolve well in water. So, when you take them by mouth, they don’t break down enough in your gut, which means people absorb less of the drug, and the results can be unpredictable. This issue is especially tough for drugs in Biopharmaceutics Classification System (BCS) Class II and Class IV—these are the ones where solubility basically controls how much your body absorbs. Because of all this, finding ways to improve how well drugs dissolve is a huge focus in pharmaceutical research. That’s where lipid-based drug delivery systems, or LBDDS, come in. In the last few years, these systems have gotten a lot of attention. They use different combinations of lipids, surfactants, and solvents to help put drugs into lipid matrices, which bumps up their solubility. Once taken, these systems can create tiny emulsions or dispersions in the gut, making way more surface area for the drug to get absorbed. On top of that, LBDDS can help drugs cross cell membranes better and even encourage lymphatic uptake, letting some drugs skip right past the liver's first-pass metabolism. That often boosts how much of the drug reaches the bloodstream. There are a bunch of types of LBDDS: liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), self-emulsifying drug delivery systems (SEDDS), and nanoemulsions. Each kind has its own set of perks. SEDDS, for example, make micro- or nano-emulsions super quickly in the gut. SLNs and NLCs do a great job controlling how fast the drug releases and keeping it stable. Liposomes stand out for being biocompatible and versatile—they can carry both water-soluble and fat-soluble drugs. LBDDS work in several ways to help the body absorb drugs better. They improve how much of the drug dissolves in the gut, speed up the dissolution rate, make the gut wall more permeable, block efflux transporters like P-glycoprotein, and tap into lymphatic transport. Put together, these mechanisms lead to better drug levels in the bloodstream and, hopefully, better therapeutic effects. Still, lipid-based delivery isn’t without its headaches. There can be stability issues, toxicity (if you need a lot of surfactants), and a real challenge scaling up production. But researchers keep finding new solutions by choosing smarter lipids, tweaking formulations, and using nanotechnology. This review will dig into all things LBDDS: how they're classified, how they're made, how they make drugs more available in the body, their pros and cons, and the latest breakthroughs. With more and more poorly soluble drugs in development, LBDDS have become a vital part of modern pharmaceutical R&D.