Evaluation Of Need For Solid Dispersion

As discussed previously, solid dispersions typically enhance the dissolution rate, and hence the bioavailability of poorly water-soluble drugs and can provide a viable path forward in the development of dosage forms for challenging NCEs. However, it must be borne in mind that compared to conventional tablet and capsule dosage forms, solid dispersion formulations are relatively complex drug delivery systems, requiring a substantially greater commitment of time, effort, and resources for...

Is Intestinal Lymphatic Transport a Factor in the Biopharmaceutical Profile of This Drug Candidate

Although intestinal lymphatic transport may not contribute significantly to the overall transport of drug from the intestine to the systemic circulation for many currently marketed oral drug products, there are a number of highly lipophilic molecules, and an increasing number of newly discovered, candidate drug compounds for which lymphatic transport does play a significant role in drug transport following oral administration. From a drug development perspective, early information as to the...

Introduction

The utility of solubilizing lipid-based formulations for improving the gastrointestinal (GI) absorption of poorly water-soluble, hydrophobic drugs is well documented in the literature (1-6). While the primary mechanism by which these formulations are thought to improve drug absorption is through elimination of the need for preabsorptive drug solubilization by the gastrointestinal tract (GIT), other mechanisms may include protection from chemical and enzymatic degradation localized in the...

Will Lipid Based Formulations Enhance the Delivery of This Drug Candidate

When initially confronted with a poorly water-soluble compound for which conventional formulation approaches aimed at improving absorption (e.g., salt or crystal form selection, particle size reduction, solid dispersions, or the addition of surfactants) has failed, the first question typically raised is, what type of formulation strategy is going to allow further development of this drug For compounds in which the primary limitation to absorption is poor aqueous solubility and slow dissolution...

Lipid Based Solid Dispersion

Many investigators have described the utility of lipid-based formulations for enhancing the bioavailability of poorly water-soluble drugs (9-12). These formulations range from simple solutions of drugs in dietary triglycerides (oil) to the use of complex mixtures of triglycerides, partial glycerides, surfactants, cosurfactants, and cosolvents to solubilize drugs. Depending on the formulation composition, they are described as nonemulsifying drug delivery systems, self-emulsifying drug delivery...

References

Intestinal cholesterol absorption. Curr Opin Lipidol 1999 10 315-320. 2. Borgstrom B. Luminal digestion of fats. In Go VL, ed., The Exocrine Pancreas. New York Raven Press, 1986 361-373. 3. Lammert F, Wang DQ. New insights into the genetic regulation of intestinal cholesterol absorption. Gastroenterology 2005 129 718-734. 4. Carey MC, Small DM. The characteristics of mixed micellar solution with particular reference to bile. Am J Med 1970 49 590-608. 5. Kannel WB, Dawber...

Solubilization Processes In The Gastrointestinal Tract

While the maximum solubility of a drug in the GIT is probably the most critical parameter controlling its absorption, decades of study have failed to identify a reliable method for consistent and accurate prediction of in vivo drug solubility. The in vivo dissolution rate and maximum solubility of a specific drug substance in the GIT is determined not only by the physicochemical characteristics of the drug substance (e.g., pKa, hydrophilicity, crystal structure, particle size, etc.), but also...

Os

Caprylic capric Triglyceride medium chain, C-8 0 C-10 0 triglycerides3'0''1 Caprylic capric Triglyceride medium chain, C-8 0 C-10 0 triglycerides3-0''1 Glycerol Mono- and di-glycerides long chain, C-18 2 monolinoleate3'0 Linoleoyl Macrogol glyceride long-chain, C-18 2 Oleic acid3 c Fatty acids C-18 l others Propylene glycol Propylene glycol di-esters of dicaprylate dicapratec C-8 0 C-10 0 fatty acids Pharmacopoeial compliance GRAS status aEuropean Pharmacopoeia, bUnited States National...

Polyglyceryl Fatty Acid Esters

The polyglyceryl fatty acid esters are composed of a chain of glycerol molecules, linked together by ether linkages, which are esterified with one or more fatty acid molecules Table 10 . For example, polyglyceryl-6 dioleate is a chain of six glycerol molecules esterified with two molecules of oleic acid. Hydrophilicity increases as the polyglycerol chain length and number of free hydroxyl groups increases and decreases with increasing number or chain length of the esterified fatty acids....

Hot Melt Extrusion

While hot melt extrusion has been used as a continuous manufacturing process in the chemical and food industry for over a century 106,107 , its commercial application in the pharmaceutical industry has been very limited. During hot melt extrusion, a mixture of drug substance and one or more excipients is continuously fed into a heated extruder barrel containing rotating horizontal screw s . The elevated temperature and high shear mixing in the barrel typically results in softening of one or...

Encapsulation Of Lipidbased Formulations

The choice of excipients, the stability of the drug, and the need for heating during the manufacturing process e.g., to enable filling of thermo-softening formulations will initially dictate the suitability of a particular capsule format SGC vs. HGC for the final product. SGCs and HGCs differ in their excipient compatibility profiles, moisture content, thermal resistance, permeability to oxygen and moisture, and need for special sealing operations. The potential impact of elevated processing...

Info

Abbreviation HPMC, hydroxypropyl methylcellulose. Abbreviation HPMC, hydroxypropyl methylcellulose. liquid-filled products 10 . While HPMC capsules are generally suitable for most nutriceutical products, limitations may be encountered in pharmaceutical application due to specific technical issues such as poor solubility at low pH or high oxygen permeability. In addition, costs are much higher than for gelatin capsules. Technical comparisons of gelatin and HPMC capsules are listed in Table 1....