Tablets formulation

Natural gums and their modified forms have been widely explored as emulsifying, suspending, binding, and disintegrating agents and as sustained-release 

Natural gum Modification Model drug Dosage form Remarks References 

Graft copolymer of GG with acrylamide by crosslinking with glutar aldehyde Verapamil and Nifedipine Hydrogel Microspheres Drug release followed non-Fickian mechanism. [47,66] 

Methacrylate acid-g-Guar gum conjugate Metronidazole Tablets In-vitro drug release with Eudragit coated L coated tablets was found to be 86.6%. The nature of drug transport was found to be non-Fickian in case of uncoated formulations, wherecis for the coated formulations, it was found to be Super Case 11 [97] 

Acetyl derivative O-acetyl- galactoglucomannan (AcGGM) was prepared BSA Hydrogel Modified AcGGM decreased the hydrolysis rate and maximum hydrolysis, indicating steric hindrance of the enzyme by the acrylate side group. [141] 

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Magnesia and aluminum suspension is useflil for the therapy of duodenal ulcers when given at high doses at frequent intervals. It is available in both hquid and tablet formulations. 

Formulation. Compressed tablet formulations contain several types of inert, adjuvant ingredients necessary for proper preparation and therapeutic performance. Tablets designed to be swallowed need diluent, disintegrating, binding (adhesive), and lubricating inert ingredients, whereas... 

Figure 4.50. Cumulative dissolution results. Two experimental tablet formulations were tested against each other in a dissolution test in which tablets are immersed in a stirred aqueous medium (number of tablets, constructional details and operation of apparatus, and amount of medium are givens). Eighty or more percent of the drug in either formulation is set free within 10 minutes. The slow terminal release displayed by formulation B could point towards an unwanted drug/excipient interaction. The vertical bars indicate ymean - with Sy 3%. A simple linear/exponential model was used to approximate the data for the strength 2 formulation. Strengths I and 3 are not depicted but look very similar.

Tablet Formulations. In this domain reported systems have been developed by personnel at Cadila Laboratories Ltd, in Ahmedabad, India, by ICI/ Zeneca/AstraZeneca in the UK, by a consortium of pharmaceutical companies in Japan, and by Pfizer UK.

The Cadila system [13] has been designed to formulate tablets for drugs based on their physical (solubility, hydroscopicity, etc), chemical (functional groups), and biologically interrelated (dissolution rate) properties. The system first identifies the desirable properties for optimum compatibility with the drug, selects those excipients that have the required properties, and then recommends proportions based on the assumption that all tablet formulations comprise at least one binder, one disintegrant, and one lubricant. Other... 

Tablet Formulations (Immediate Release). Two papers in the mid-1990s reported the earliest studies on immediate release tablets. In the first, tablet formulations of hydrochlorothiazide [33] were modeled in an attempt to maximize tablet strength and select the best lubricant. In the other, a tablet formulation of caffeine was modeled [34] to relate both formulation and processing variables with granule and tablet properties.

In a series of papers, personnel from Novartis and the University of Basel in Switzerland have highlighted the pros and cons of neural networks for immediate release tablets [37-40]. In other studies neural networks have been found useful in modeling tablet formulations of antacids [41], plant extracts [42], theophylline [43], and diltiazem [44]. In a recent paper Lindberg and Colbourn [45] have used neural networks, genetic algorithms, and neurofuzzy to successfully analyze historical data from three different immediate-release tablet formulations. 

Tablet Formulations (Controlled Release). In this domain, the first studies were carried out in the early 1990s by Hussain and coworkers at the University...

Rowe RC, Craw S, Wiratunga N. Case-based reasoning—a new approach to tablet formulation. Pharm Tech Eur 1999 ll(2) 36-40. 

Kesavan JG, Peck GE. Pharmaceutical granulation and tablet formulation using neural networks. Pharm Dev Technol 1996 1 391-404. 

Colbourn EA, Rowe RC. Modelling and optimization of a tablet formulation using neural networks and genetic algorithms. Pharm Tech Eur 1996 8(9) 46-55. 

Rowe RC, Colbourn EA. Generating rules for tablet formulations. Pharm Tech Eur 2000 12(l) 24-7. 

Lindberg N-O, Colbourn EA. Use of artificial neural networks and genetic algorithms—experiences from a tablet formulation. Pharm Tech Eur 2004 16(5) 35-9. 

G. Levy and R. H. Gumtow, Effect of certain tablet formulation factors on dissolution rate of the active ingradient. III. Tablet lubricants, J. Pharm. Sci., 37. 52,1139-1141 (1963). 

White, Effect of certain tablet formulation factors on 38. dissolution rate of the active ingredients. II. Granule... 

The phenomenon of pseudopolymorphism is also observed, i.e., compounds can crystallize with one or more molecules of solvent in the crystal lattice. Conversion from solvated to nonsolvated, or hydrate to anhydrous, and vice versa, can lead to changes in solid-state properties. For example, a moisture-mediated phase transformation of carbamazepine to the dihydrate has been reported to be responsible for whisker growth on the surface of tablets. The effect can be retarded by the inclusion of Polyoxamer 184 in the tablet formulation [61]. 

Table 5 Some Multiple-Use Excipients for Tablet Formulation... 

The influence of the actual manufacturing process can also affect the contribution of the diluent to the final characteristics of the product. For instance, Shah et al. [45] demonstrated that the release of drug from tablets formulated with soluble excipients may be more... 

Some tablet formulations call for the inclusion of a small amount of semisolid, or even semiliquid, ingredient. It is highly desirable that any such component should be adsorbed onto, or absorbed into, one of the powders. In cases where none of the other excipients in the formulation is able to act as a carrier, an... 

In order to produce an adequate tablet formulation, certain requirements, such as sufficient mechanical strength and desired drug release profile, must be met. At times this may be a difficult task for the formulator to achieve, due to poor flow and compactibility characteristics of the powdered drug. This is of particular importance when one only has a small amount of active material to work with and cannot afford to make use of trial-and-error methods. The study of the physics of tablet compaction through the use of instrumented tableting machines (ITMs) enables the formulator to systematically evaluate his formula and make any necessary changes. 

The ultimate challenge for tablet formulators in the twenty-first century is to achieve a true understanding of material properties and material science. Those who can quickly conceive a compatible, functional formulation will be irreplaceable as large companies shrink their R D resources and the public sector demands better efficiency. 

Hard gelatin capsules are uniquely suitable for blinded clinical tests and are widely used in preliminary drug studies. Bioequivalence studies of tablet formulations may be conveniently blinded by inserting tablets into opaque capsules, often along with an inert filler powder. Even capsule products may be disguised by inserting them into larger capsules. 

Capsule formulations usually require lubricants just as do tablet formulations. Lubricants ease the ejection of plugs, reduce filming on pistons and adhesion of powder to metal surfaces, and reduce friction between sliding surfaces in contact with powder. The same lubricants are used in both tablet and capsule formulations. 

GS Rekhi, ND Eddington, MJ Fossler, P Schwartz, LJ Lesko, LL Augsburger. Evaluation of in vitro release rate and in vivo absorption characteristics of four metoprolol tartrate immediate release tablet formulations. Pharm Devel Tech 2(1) 11-24, 1997. 

AD Koparkar, LL Augsburger, RF Shangraw. Intrinsic dissolution rates of tablet filler-binders and their influence on the dissolution of drugs from tablet formulation. Pharm Res 7 80-86, 1990. 

This optimization method, which represents the mathematical techniques, is an extension of the classic method and was the first, to our knowledge, to be applied to a pharmaceutical formulation and processing problem. Fonner et al. [15] chose to apply this method to a tablet formulation and to consider two independent variables. The active ingredient, phenylpropanolamine HC1, was kept at a constant level, and the levels of disintegrant (corn starch) and lubricant (stearic acid) were selected as the independent variables, X and Xj. The dependent variables include tablet hardness, friability, volume, in vitro release rate, and urinary excretion rate in human subjects. 

The system selected here was also a tablet formulation. The five independent variables or formulation factors selected for this study are shown in Table 2. The dependent variables are listed in Table 3. Since each dependent variable is considered separately, any number could have been included. 

Designed experimentation, involving mostly some type or modification of factorial design, has been used to study many different types of formulation problems. These include a pharmaceutical suspension [21], a controlled-release tablet formulation [22], and a tabletcoating operation [23]. In the latter case, Dincer and Ozdurmus studied an enteric film coating and utilized the steepest descent graphic method to select the optimum. 

Other applications of the previously described optimization techniques are beginning to appear regularly in the pharmaceutical literature. A literature search in Chemical Abstracts on process optimization in pharmaceuticals yielded 17 articles in the 1990-1993 time-frame. An additional 18 articles were found between 1985 and 1990 for the same narrow subject. This simple literature search indicates a resurgence in the use of optimization techniques in the pharmaceutical industry. In addition, these same techniques have been applied not only to the physical properties of a tablet formulation, but also to the biological properties and the in-vivo performance of the product [30,31]. In addition to the usual tablet properties the authors studied the following pharmacokinetic parameters (a) time of the peak plasma concentration, (b) lag time, (c) absorption rate constant, and (d) elimination rate constant. The graphs in Fig. 15 show that for the drug hydrochlorothiazide, the time of the plasma peak and the absorption rate constant could, indeed, be... 

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