Case studies in drug delivery

Most of the change we think we see in life Is due to truths being in and out of favour. 

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Infusion of fat into the ileum has been shown to cause a lengthening of the SITT—a phenomenon known as the ileal brake (27,28). However, the effect is generally modest (causing a delay of 30-60 min) and attempts to exploit this mechanism in drug delivery have had limited success. Dobson et al. (29,30) studied the effect of co-administered oleic acid on the small intestinal transit of non-disintegrating tablets. They showed a delay in SITT in over half of all cases, and a doubling of SITT in some instances, but in the other cases SITT was either unaffected or even reduced. Lin et al. (31) have also showed slowed GI transit in patients with chronic diarrhea by administration of emulsions containing 0, 1.6, and 3.2 g of oleic acid. Small intestinal transit in normal subjects was measured at 102 11 min, while the transit times in the patients treated with the three emulsions were, respectively, 29 3, 57 5 and 83 5 min. 

Wall, D.A. Smith, P.L. Inhalation therapy for growth hormone deficiency. In Inhalation Delivery of Therapeutic Peptides and Proteins Adjei, A.L., Gupta, P.R., Eds. Marcel Dekker, Inc. New York, 1997 453-469, Ch. 16. Patton, J.S. Platz, R.M. Routes of dehvery case studies (2) pulmonary delivery of peptides and proteins for systemic action. Adv. Drug Deh. Rev. 1992, 8, 179-186. 

Topical Formulations. Topical formulations by their very nature are usually multicomponent, and it is not surprising that neural networks have been applied to deal with this complexity. The first work was performed on hydrogel formulations containing anti-inflammatory drugs in Japan in 1997 [57], followed up by further studies in 1999 [58] and in 2001 [59]. Lipophilic semisolid emulsion systems have been studied in Slovenia [60, 61] and transdermal delivery formulations of melatonin in Florida [62]. In all cases, the superiority of neural networks over conventional statistics has been reported. 

Aliphatic polyesters based on monomers other than a-hydroxyalkanoic acids have also been developed and evaluated as drug delivery matrices. These include the polyhydroxybutyrate and polyhydroxy valerate homo- and copolymers developed by Imperial Chemical Industries (ICI) from a fermentation process and the polycaprolactones extensively studied by Pitt and Schindler (14,15). The homopolymers in these series of aliphatic polyesters are hydrophobic and crystalline in structure. Because of these properties, these polyesters normally have long degradation times in vivo of 1-2 years. However, the use of copolymers and in the case of polycaprolactone even polymer blends have led to materials with useful degradation times as a result of changes in the crystallinity and hydrophobicity of these polymers. An even larger family of polymers based upon hydroxyaliphatic acids has recently been prepared by bacteria fermentation processes, and it is anticipated that some of these materials may be evaluated for drug delivery as soon as they become commercially available. 

Macleod et al. [92] have studied the potential of pectin-chitosan-hydroxypropyl methylcellulose films for colonic drug delivery [92]. The results showed that in all cases the tablets were able to pass through the stomach and small intestine intact. The tablets started to break up once they were in the colon, due to degradation of the coat by colonic bacteria. 

Numerous cases exist in the pharmaceutical field in which pH control of drug delivery may be beneficial. For example, the ability to store a drug molecule in the dry state in a polymer, to be released when the polymer reaches a region in the gastrointestinal tract that is characterized by a certain pH range (acidic in stomach, alkaline in the small intestine) has prompted a number of researchers to study pH-sensitive polymer gels as potential drug carriers for oral delivery [1-4]. 

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