Drug property improvement

Corticosteroids have potent anti-inflammatory properties and are used in active IBD to rapidly suppress inflammation. Corticosteroids have favorable effects in modulating several cell types involved in the inflammatory process.20,21 They may be administered systemically or delivered locally to the site of action by altering the drug formulation (Table 16-2). Because these drugs usually improve symptoms and disease severity rapidly, they should be restricted to short-term management of active disease. Long-term use of systemic corticosteroids is... 

Although tobacco Nicotiana tabacum) is widely known for its stimulant and addictive properties, its principal psychoactive constituent, nicotine, has become a candidate drug for improving cognition (Le Houezec 1998 Lawrence and Sahakian 1998 Newhouse et al. 1997). Clearly, the health risks associated with smoking tobacco preclude its clinical use, but nicotine delivered in other forms may be useful. 

The group of organic bases known as alkaloids (B-81MI10603) includes the active principles of some of the oldest remedies used in folk medicine, and many of them still have important uses. The manufacture of such compounds by total synthesis is usually unattractive, but some, for example morphine, undergo chemical manipulation to give drugs with improved properties, and some have served as models for simpler synthetic compounds. 

Another way of describing the L T ratio concept is that of pulmonary targeting. Drug properties that improve pulmonary targeting include slow absorption from the lungs, low oral systemic availability, and rapid systemic clearance. 

Anderson, B. D. 1980. Thermodynamic considerations in physical property improvement through prodrugs. In Physical Chemical Properties of Drugs, edited by S. H. Yalkowsky, A. A. Sinkula, and S. C. Valvani, 231-266. NewYork Marcel Dekker, Inc. 

Figure 2.7 N-lsopropyl-thiadiazolyl sulfanilamide (IPTD) 19 was the first sulfonamide that showed antidiabetic properties in the clinics. Carbutamide 20 and tolbutamide 21 are also antidiabetics tolbutamide 21 has a shorter biological half-life than carbutamide 20, due to its methyl group instead of the chlorine atom in addition, tolbutamide does not show antibacterial activity. Glibendamide 22 is an antidiabetic drug with improved therapeutic properties.

To develop platinum drugs with improved properties compared to cisplatin, a plethora of cisplatin analogs have been designed with appended additional ftmctionalities. The rationale is that these incorporated moieties could lead to a host of favorable pharmacokinetic properties, such as targeting to cancer cells, improved transport into the cell, and increased affinity for DNA. Furthermore, to overcome the problem of resistance, pendant DNA interacting moieties have been... 

Both of these objectives are achievable provided the delivery (transport) properties of the drug are improved while maintaining its biological activity in vivo. In this context, the parent drug properties, such as lipid solubility, aqueous solubility, partition coefficient, and chemical and metabolic stability, are optimized, often in a balanced combination. 

Hypromellose phthalate may be used alone or in combination with other soluble or insoluble binders in the preparation of granules with sustained drug-release properties the release rate is pH-dependent. Since hypromellose phthalate is tasteless and insoluble in saliva, it can also be used as a coating to mask the unpleasant taste of some tablet formulations. Hypromellose phthalate has also been co-precipitated with a poorly soluble drug to improve dissolution characteristics. 

An immediate improvement in the drug properties could be obtained by the replacement of the sulfamido group with a more lipophilic group such as halogen. Compound (70) inhibited apomorphine-induced stereotypy in rats at a 30-fold lower dose than sulpiride (330). Whereas the racemic 2,6-di-methoxy derivative (71) was equipotent with sulpiride against apomorphine mediated behaviors, the S-enantiomer of the 3-bromo-2,6-dimethoxy derivative (remoxipride) (72) closely resembled haloperidol in its ability to block apomorphine-induced hyperactivity. The sevenfold ratio of stereotypy to hyperactivity for remoxipride suggested a low propensity to produce EPS in the clinic. Remoxipride was briefly used in clinical practice, but the development of aplastic anemia in a minority of patients led to its eventual withdrawal (331). 

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