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Key Point of Dry Powder Injection

The injectable dry filling area is a completely sterile area of the company that is a strictly controlled area. The high-level alertness is mandatory to main the atmospheric condition in the filling area of the dry powder filling area of Injectable. Every step in the production area requires a written SOP. It is very important to check the relative humidity and temperature of the filling room to avoid any quality issues with the product. The best way to address the requirement of conditions an approved SOP for dry powder filling operation should be followed.

Powders for injection (PIs) constitute an important category of dosage forms for active molecules. Because of
their instability in the aqueous environment, PIs cannot be marketed as ready-to-use injectables

(1). Instead, they are marketed as dry powders to be reconstituted with a suitable vehicle just before administration. The final form after reconstitution may be either a solution or a suspension

(2). Typical molecules in this category include

Beta-lactam antibiotics, cephalosporins, and acyclovir. A few ready-to-use infusion products are marketed as frozen solutions in plastic bags for these molecules. However, the low temperature required for their shipment and storage makes these products an unviable option, especially in countries in which a cold chain from manufacturing to the point of consumption is difficult to establish.
Depending on their formulation strategy, PIs can be categorized into any of the classes . Two strategies can be adopted for the formulation and manufacture of PIs The first strategy of lyophilizing the primary pack allows the formulation of drugs that are thermolabile or unstable in aqueous solution. However, lyophilization normally yields an amorphous or partially amorphous product, which leads to solid-state instability

(3). A more-stable crystalline stage can be obtained by crystallization in aseptic conditions, and it can be maintained by directly filling the sterile dry-powder drug into presterilized vials , Strategy
2). The dry-filling process also is much more cost effective because it requires less infrastructure as well as a reduced amount of energy and a shorter amount of time to produce a batch

(4). These reasons have made dry-filled PIs a popular dosage form.
A PI formulation may consist of drug only or drug plus excipient. Table I lists a few examples of formulations containing functional excipients.

Variables Affecting Reconstitution Time of Dry Powder for Injection

A number of drugs are unstable in an aqueous environment, even when exposed for a short duration, thus requiring packaging, storage, and shipping in a powder or lyophilized state to keep the product stable during its shelf life. Used for parenteral administration, these drugs are commonly known as powder for injection (PI), powder for reconstitution, dry powder injection, or powder for constitution. USP 43 describes more than 100 drugs available as dry powder for injection.

Intrinsic parameters affecting reconstitution time

Intrinsic parameters are inherent to an active pharmaceutical ingredient (API) or a formulation and include the molecular-, particle-, and bulk-level solid-state properties of the API. Any added excipients also influence the inherent reconstitution properties of the product.

Particle-size distribution. Powder dissolution is a kinetic phenomenon that depends primarily on the surface area exposed to the solvent, which in turn is a function of particle size. Particle size, therefore, influences reconstitution time.

Intrinsic parameters affecting reconstitution time

Intrinsic parameters are inherent to an active pharmaceutical ingredient (API) or a formulation and include the molecular-, particle-, and bulk-level solid-state properties of the API. Any added excipients also influence the inherent reconstitution properties of the product.

Particle-size distribution. Powder dissolution is a kinetic phenomenon that depends primarily on the surface area exposed to the solvent, which in turn is a function of particle size. Particle size, therefore, influences reconstitution time.

Porosity. The porosity of dry powder may have a significant effect on its reconstitution. Haeger et al. showed that an increase in porosity of the lyophilized cake by decreasing the concentration of the fill solution before lyophilization yielded a fluffy, low-bulk density lyophilized parenteral formulation with the desired characteristic of rapid reconstitution time.

Solid-state form. A drug can exist in crystalline, solvate, or amorphous form. Polymorphism, the existence of several crystalline forms of a single compound, affects dissolution properties of the drug

Degree of crystallinity. The degree of crystallinity, which is the percentage of crystalline form of any compound in the amorphous matrix, can markedly affect dissolution properties. Analytical techniques used to determine the degree of crystallinity include powder X ray diffractometry , near infrared spectroscopy , Raman spectrometry , solid-state nuclear magnetic resonance , dynamic vapor sorption , and thermo analytical techniques such as isothermal microcalorimetry , differential scanning calorimetry , modulated temperature differential scanning calorimetry , and solution calorimetry . Reliability of the results may improve if several techniques are used in parallel.

Formulation factors. The inherently low aqueous solubility of an API in formulation may contribute to incomplete reconstitution. Several formulation interventions are used in such instances, including the use of cosolvents, cyclodextrin complexation, lipidic systems, and amorphization by freeze drying.

Degradation products. The presence of excess moisture in the formulation can sometimes accelerate chemical and physical degradation, which results in the formation of less-soluble degradation products that slow the reconstitution process.

Foaming. Foaming during reconstitution is a serious problem for biopharmaceutical drugs because it may lead to protein denaturation and a consequent loss in their activity. This situation necessitates determination of the protein activity that is lost as a result of shaking, which may further assist in setting specifications for reconstitution time

 

 

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