Issue link: http://www.e-digitaleditions.com/i/793410
pulmonary delivery—two-piece (hard) capsules are play- ing a leading role. This article summarizes important developments in hard capsules over the last 10 years, including the most recent innovation: A non-gelatin cap- sule that offers enteric protection and delayed release without using a functional coating. Controlled- and targeted-release formulations Targeting the upper small intestine for release can lead to high local API levels and rapid absorption, while tar- geting the colon can help treat irritable bowel syndrome, ulcerative colitis, and other disease states. Depending on whether delayed release or site-specific targeting is required, there are three main approaches: timed release, pH-controlled release, and enzymatic release. Timed release formulations use functional coatings that erode slowly, independent of pH, or they include a matrix that releases the active as the matrix erodes or when erosion is complete. With pH-controlled release, formulators take advantage of the increase in pH going from the stomach to the small intestine and use an enteric polymer coating with an appropriate profile. The coating renders the dosage form insoluble at the lower pH of the stomach to upper small intestine, yet soluble at the higher pH of the distal small intestine. Enzymatic release uses starch-based coatings that resist digestion in the stomach and small intestine, but are degraded by micro- bial enzymes when the dosage form reaches the colon. Early HPMC capsules Capsules are widely used to administer both solid and liquid drug products. Most hard capsule shells are made of gelatin or hydroxypropyl methylcellulose (HPMC). This latter polymer emerged nearly two decades ago to meet the need for a non-animal-derived alternative to gelatin. In addition, HPMC is more compatible with 18 March 2017 Tablets & Capsules Figure 1 pH 1.2 USP pH6.8 USP pH 6.8 JP2 Simulated milk fluid pH 1.2 - 2 g KCI/L pH 1.2 - 9 g KCI/L pH 1.2 USP pH6.8 USP pH 6.8 JP2 Simulated milk fluid pH 1.2 - 2 g KCI/L pH 1.2 - 9 g KCI/L Comparison of dissolution performance of HMPC capsules made with and without gelling agents b. In vitro dissolution of caffeine filled into HPMC capsules made without gelling agents (Vcaps Plus). a. In vitro dissolution of caffeine filled into HPMC capsules made with gelling agents (kappa-carrageenan and potasium chloride). 0 3 6 9 12 15 18 21 24 27 30 35 40 45 50 55 60 75 0 3 6 9 12 15 18 21 24 27 30 35 40 45 50 55 60 75 100 90 80 70 60 50 40 30 20 10 0 100 90 80 70 60 50 40 30 20 10 0