Suspension products

In the case of suspension products of this type, the function should be considered based on the particle size of the active ingredient. The combination of active ingredient, propellant, co-solvent, and surfactant should be investigated. Potential for extraction and other interactions with the container system parts (including the valve mechanism) should be reported. 

Where there is a dosing device provided with the product, the dose reproducibility and accuracy should be demonstrated. Examples include dropper devices, dose-measuring devices, and pen injectors. The instructions for use should also be discussed for such devices and may be particularly important for devices such as two-chamber cartridges and the like containing suspension products. It might be necessary to discuss how dosing devices meet the relevant Essential Requirements of the Medical Device Directives with reference to appropriate and relevant harmonized and other European (EN) and International Standards Organization (ISO) standards. 

There are two EPARs for eyedrops. Specific issues considered for these include container composition and tamper evidence, the optimization of the formulation and manufacture, preservative and preservation issues, and justification for the use of nonterminal sterilization processes. Many of the points concerning active ingredients and excipients are similar to those discussed above. Changes in formulation during the development process (e.g., for carbomers or surfactants) are mentioned. Particle size controls for suspension products are discussed. 

A number of oral solution or suspension products are included in the EPARs. Apart from the usual points of consideration for active ingredients and excipients, particular mention is made of possible precipitation of active ingredient when a solution is in use, the inclusion of excipients having a major impact on bioavailability, the need for flavoring to mask the taste of the active ingredient, relative potency compared with other routes of administration, preservation issues, dosing devices and the precision and accuracy of the dose delivered, and bioequivalence where formulations have been modified during the development process. 

Upon determination of design settling velocity, one must choose the scale of agitation required using Table 5 (9), which serves as the suspension products equivalent of Table 3. 

Polysorbate 80 is widely used as a nonionic surfactant in liquid pharmaceutical products such as inhalation, suspension, and nasal suspension products, due to its properties of solubilization, reduction of surface and interfacial tension, and wetting. Direct analysis of Polysorbate 80 is quite time consuming. Size-exclusion chromatography (SEC) has been reported [5] in which a mobile phase contained the surfactant at concentrations above the critical micelle concentration. Polysorbate 80 appeared as a very broad peak and coeluted with other peaks, which makes quantification in Nasonex impossible. 

Process flowcharts. A flow diagram should indicate the process steps and addition of raw materials. If possible, major equipment and special environmental conditions may be included in the flowchart. In-process tests may also be included. A second flowchart for activities, raw material suppliers, shipments, and testing would also assist in the overall picture of the aerosol manufacturing scheme, especially for multiple site or third-party activities. An example of a process flowchart for a fictitious suspension product (2160.4-kg batch size for 100,000 units) is shown in Figure 6. 

Cell Harvesting and Cell Suspension Production, 3.2. Density Gradient Separation, and 3.3. Cell Detection Through Immunocy-tochemistry. 

Bioequivalence or Clinical Study In the patient, the general or systemic circulation is responsible for carrying molecules to different tissues of the body. To assure the expected bioactivity of a product, the amount of drug that reaches the systemic circulation per unit of time is analyzed and is known as bioavailability. Bioequivalence is the comparison of the bioavailability of a product with a reference product. While oral solutions may not always need bioequivalence studies because they are considered self-evidente, suspensions usually require bioequivalence or clinical studies in order to demonstrate effectiveness. However, OTC suspension products such as antacids are exempt from these studies [6]. 

The traditional era of the solution-only dosage form for use in the eye ended in the 1950s with the availability of suspension dosage forms. Solid drug particles of cortisone acetate were first suspended and a suspension product commericialized. In an imorthodox approach, for the first time clinical studies revealed that a sufficiently reduced particle sized drug could be instilled on... 

Suspension products (Table 4) are prepared by combining sterile vehicle and sterile drug powder asepti-cally or by combining two sterile solutions, with the drug solution precipitating in the diluent solution. 

As in the case of the BDP solution aerosol, enhanced efficiency of aerosolization, leading to high lung deposition compared with an equivalent suspension product. 

Solution products can be more susceptible to drug losses into the elastomeric components of the valve than for an equivalent suspension product. Drug losses of this kind can be an issue particularly for low dose products. 

More recently, other (less volatile) organic modifiers, e.g., glycerol, have been added to solution-based HFA MDIs to modify the particle size distribution so that it more closely resembles that of the originator suspension product. ... 

Decrease Suspension products Mask taste Slow drug release Increase melting point Use hydrophobic counterions Reduce acidity of conjugate acid (>pAa)... 

Table 7 is a current listing of parenteral suspension products. 

Physical stability is also an issue. Farmers do not have the time to premix individual doses of suspensions, nor constantly shake the bottle between administrations to some several hundred individual cows of their herd. Thus, for example, in the case of suspensions, the final product physical characteristics are often a balance between retardation of sedimentation and ease of flow to draw up into the syringe. Thus a critical evaluation of existing suspension products by a formulation scientist new to the field may draw false conclusions as to the need for an improved product based on ease of administration since there is more than pharmaceutical elegance involved in developing the perfect veterinary formulation. Indeed, a farmer is less interested in what the product looks like compared with its efficacy profile, ease of use, ease of administration, ease of removal, tissue residue profile, and time it takes to herd, administer, and release his animals back into the paddock. Veterinary formulation scientists may therefore trade off pharmaceutical elegance to improve other features, provided the efficacy and safety profile is acceptable and not altered during storage. 

Stability) will eventually decrease. Similarly, if a metastable polymorph is used to formulate a suspension product, aggregation will be found on standing. However, if a stable polymorph with a low energy level is used, a stable suspension may result. The physical stability of a suspension may be determined by observing the column height of the suspension in a graduated cylinder. 

Particle Size. For substances to be used in certain formulations such as solid or suspension products, the particle size can have a significant effect on dissolution rates, bioavailability, and stability. A decision tree in the guideline provides guidance as to when particle size testing should be considered. 

Suspension products may pose challenges to the formulator in manufacturing to achieve a sterile product. The possibilities of either degradation or morphological changes occurring during the sterilisation process exist and must be prevented. 

If the drug is insufficiently soluble to allow delivery of the required dose as a solution (the maximum delivered dose for each nostril is 200 p,L), then a suspension formulation will be required. There are additional issues for suspension products, for example crystal growth, physical stability, resuspension, homogeneity and dose uniformity. Suspension products will also require information on density, particle size distribution, particle morphology, solvates and hydrates, polymorphs, amorphous forms, moisture and/or residual solvent content and microbial quality (sterile filtration of the bulk liquid during manufacture is not feasible). 

The stability studies for drug injectable suspension and drug for injectable suspension products should also include particle size distribution, redispersibility, and rheological properties in addition to the parameters cited above for drug injection and drug for injection products. 

UPPER SUSPENSION PRODUCT SCOOP ROTATING baffle ROTOR... 

For suspension products, sample must be uniform prior to measurement. The cleaning of the electrode after each sample is important, especially if the suspension contains a high level of taste-masking agents, such as sugars. The pH electrode can easily become coated with particles or viscous liquids that hinder performance. When working with suspensions, as compared with solution products, the number of samples tested within a bracket should be reduced. 

STEPAN TAB-2 FUKE DI(HYDROGENATED) TALLOW PHTHALICACID AMIDE Flake Emulsion and suspension product for triglycerides, mineral oi, and silicones. 

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