Injectable drug formulations

A partieular methylated pCD, the heptakis (2,6-di-O-methyl-pCD, ealled DIMEB) is a erystalline produet. It is extremely soluble in eold water but insoluble in hot water, therefore, its purifieation, and also the isolation, of its complexes is teehnieally simple. Up to now, no better solubilizer was found among the CDs. It is available in better than 95% isomerie purity for injectable drug formulation. but for widespread industrial applieation, the cheaper randomly methylated pCD (called RAMEB) is produced and marketed. 

Controlled drug delivery ean be an important factor when traditional oral or injectable drug formulations eannot be used. A wide range of materials have been employed to eontrol the release of drugs and other active agents, although polymeric systems are the most common because of their desirable physical properties [94]. 

Various coUoidal systems formed with block or graft copolymers, such as liposomes, microspheres, emulsions have been described for oral drug-delivery systems. Block and graft copolymers in their micellar form or as steric stabilizers for colloidal particles are well suited for oral and injectable drug formulations and diagnostic systems if they meet the requirement of biocompatibility and preferably of biodegradability [278,279]. 

Besides the inhalative use, the development of a drug formulation for A9-THC has to address other bioavailabihty questions. A major problem is the hpophiUcity and poor solubiUty in water, hmiting oral uptake when given orally. Because of this, other parenteral routes of apphcation are imder investigation like puhnonal uptake by vaporization, subUngual or intranasal administration, and apphcation by injection of A9-THC incorporated in hpo-somes. 

Sterility, freedom from pyrogens, and acceptably low level of extraneous particulate matter are critical quality attributes of all injectable products. Additional critical quality attributes depend on the clinical use of the product. For example, for IV, IM, and SC routes, isotonicity and physiological pH (7.4) are always desirable in order to minimize potential irritation upon injection. Other factors may preclude this, however. If the required dose of drug must be administered in a small volume, it may not be feasible to formulate an isotonic solution. Likewise, solubility or stability considerations may preclude formulation at physiological pH. This explains why formulation pH for injectable drugs varies from about pH 2 to about pH 11. 

Accuracy is defined as the bias of the method, it is a measure of how close the observed result is to the specified quantity. It is usually tested using a method of spiked placebos or of standard addition [3,4]. The expected performance of a method with respect to its accuracy varies enormously from sample to sample. A simple drug formulation, such as a tablet or injection, assayed by HPLC can expect an accuracy of around +/- 1%. 

Figure 1 Sequential biodistribution of various formulations of injectable drugs.

Early development of polymers in injectable drug delivery primarily involved PLA and poly(lactic-co-glycolic) acid (PLGA) due to the prior use of these polymers in biomedical applications as sutures. Besides the safe and biocompatible nature of these polymers, their ease of availability made them ideal first candidates for screening parenteral CR formulations. Some of the early biodegradable polymer-based products for injectable sustained release used these polymers. However because... 

Many drugs can now be delivered rectally instead of by parenteral injection (intravenous route) or oral administration. Generally, the rectal delivery route is particularly suitable for pediatric and elderly patients who experience difficulty ingesting medication or who are unconscious. However, rectal bioavailabilities tend to be lower than the corresponding values of oral administration. The nature of the drug formulation has been shown to be an essential determinant of the rectal absorption profiles. The development of novel absorption enhancers with potential efficacy without mucosal irritation (low toxicity) is very important. The delivery of peptide and protein drugs by the rectal route is currently being explored and seems to be feasible. 

Bioavailability studies quantify rate and extent of absorption. They compare the efficiency of the disposition of several drug formulations, e.g. immediate-release vs. extended-release or capsule vs. tablet or tablet A vs. tablet B etc., or they compare the disposition of different routes of administration, e.g. oral vs. subcutaneous or oral vs. intravenous. According to the definition, a comparison to the intravenous bolus injection yields the absolute bioavailability. 

Development of drug formulation Development of tablets, syrups, injectables, and so on, containing the drug substance... 

Think about drug formulation. Is a tablet the most appropriate form of drug or would an injection, a suppository or a syrup be better Is the drug suitably packaged for the elderly patient, bearing in mind any disabilities ... 

Mixing drugs formulated for injection in a syringe may cause interaction, e.g. protamine zinc insulin contains excess of protamine which binds with added soluble insulin and reduces the immediate effect of the dose. 

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