Tableted drug delivery systems

Zavos, P. M., Correa, J. R., and Zarmakoupis-Zavos, P. N. (1998), Assessment of a tablet drug delivery system incorporating nonoxynol-9 coprecipitated with polyvinylpyrrolidone in preventing the onset of pregnancy in rabbits, Fertil. Steril., 69, 768-773. 

Tiltabs. Tiltab tablets represent one of the few dosage formulations that has been developed expressly to meet the needs of patients with impaired dexterity [185], Marketed by Smith, Kline French Laboratories, Ltd. in several European countries, the novelty of the Tiltab design is its irregular shape that prevents it from lying flat. Apparently, tablets manufactured in this fashion are easier to handle by those with impaired dexterity. Moreover, these tablets are readily identifiable by patients so that differentiation from other medication is facilitated. Other innovations like this are needed for drug-delivery systems with the particular needs of the geriatric patient in mind. 

Drug-delivery systems are essentially specialized dosage forms developed to overcome the limitations of conventional dosage forms, such as simple tablets, capsules, injectable solutions, etc. Some of the reasons behind the development of oral DDSs are listed below ... 

Pharmaceuticals, for the purpose of this book, means chemical compounds that are used in pharmaceutical production. This can comprise the active ingredient, which is also called active pharmaceutical ingredient (API) or drug substance or drug product and the inert pharmaceutical ingredients (excipients) that are used to formulate a drug product in the form of tablets, capsules, ointments, creams, lotions, parenterals, inhalers, and a variety of drug delivery systems. 

A buccal drug delivery system is applied to a specific area on the buccal membrane. Moreover, the delivery system ean be designed to be unidirectional in drug release so that it can be protected from the loeal environment of the oral cavity. It also permits the inclusion of a permeation enhancer/protease inhibitor or pH modifier in the formulation to modulate the membrane or the tablet-mucosal environment at that particular application site. While the irritation is limited to the well-defined area, the systemic toxicity of these enhancers/inhibitors and modifiers can be reduced. The buccal mucosa is well suited for this type of modification as it is less prone to irreversible damage [9]. In the event of drug toxicity, delivery can be terminated promptly by removal of the dosage form. 

There are few occasions where a drug is delivered alone in a pure form into the body, but it is usually combined with other materials (called excipients) to form drug delivery systems ( medicines , formulations or dosage forms ). These promote accurate dosing, therapeutic effectiveness, stability and patient acceptability. By far the most common route for delivering drugs into the body is by the oral route, swallowing a tablet or capsule. 

In order to reduce further the ketoprofen release rate from matrix tablets, the partial coating of the cores with CAP was assayed. This technique was successfully applied to obtain a progammable zero-order drug delivery system [5]. 

Solid oral dosage forms containing new chemical entities (NCEs) are commonly formulated into tablets or capsules as their first market image formulation. Subsequent drug product line extension development on these NCEs may evaluate more specialized drug delivery systems. Dissolution testing of standard oral tablets or capsules will commonly utilize the paddle or basket apparatus. In this chapter we focus primarily on the development and subsequent validation of dissolution testing methods that use these two devices. 

We include certain excipients in a formulation specifically because they interact with the physiological fluids and the bodily functions in a certain way. For example, as discussed above, we include disintegrants in immediate release tablet and capsule formulations, because we know that when they encounter the aqueous environment of the stomach, they will cause the tablet or capsule to disintegrate and thereby aid dissolution of the API. Another example is the general case of hydrophilic colloid matrices used as prolonged release drug delivery systems. We know that when these materials contact the aqueous environment of the GIT they swell and create a diffusion barrier that slows the rate of dissolution of the dissolved drug. 

Some questions a formulator needs to address up front are What are the marketing plans What are the potential obstacles to uniformity Is the active raw material physically and chemically consistent What are the physical plant constraints Addressing these and other questions in the early stages of development could aid in avoiding many scale-up nightmares. Additionally, the identification of potential scale-up issues forces the formulator to consider commercialization of the drug delivery system. Too often, formulation scientists develop tablet formulations in a bubble, only to be later handed off to some poor process development person who has to make it work. 

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 fordevelopment. Therefore, whetherthere is a need forsolid dispersion and whetherthi... 

FIGURE 22.15 Pharmacokinetic parameters for the Spherazole CR tablet, 100 mg, compared with the Sporanc IR capsule. (Note Types A and B differed in levels of rate-controlling excipients.) (Adapted from Jacob, J. Gastroretentive, bioadhesive drug delivery system for controlled release of itraconazole pharmacokinetics of Spherazole CR in healthy human volunteers. Controlled Release Society 34th Annual Meeting and... 

Sustained adhesion of the dosage form (tablet, patch) to the mucosa is an important first step to successful buccal delivery. The mucus plays an important role during this mucoadhe-sive process by buccal drug delivery systems. The interaction between the mucus and mucoadhesive polymers generally used in most dosage forms can be explained by theories summarized in Table 9.1. 

For a very long time, scientists generally underestimated the importance of excipients in pharmaceutical dosage forms. Excipients were cheap ingredients viewed solely as inert supports for medicaments. Today, with modern pharmaceutical excipients on the shelf, development of various novel drug delivery systems, and production with high-speed tablet/capsule machines, excipients are rather more than the sugar in the pill.9,10... 

An API is closely controlled in terms of crystal form, polymorph identity, particle size, impurity profile and content, solvent, and water levels. All of these quality parameters are defined in creating a drug product that has the desired pharmacological properties (e.g., tablet dissolution rate to give needed blood levels) and desired physical properties (e.g., stability and compatibility with drug delivery systems). 

Carbopol resins also have been used in controlled-release dosage forms. Especially, the resins Noven AA-1 USP and Carbopol 934P NF are being extensively developed in bioadhesive drug delivery systems for topical, bucal or nasal, ocular, and rectal applications (e.g., Fentanyl ). Noven CA-1 USP and CA-2 USP are used as oral laxative and antidiarrheal products in swallowable and chewable tablets. 

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