The impact of physical properties of API on pre-prescription studies of injectables

People may take medicine when they catch a cold daily; some take tablets, and some take capsules; these tablets and capsules are pharmaceutical preparations. Pre-prescription study of drug formulation is the understanding, analysis, utilization, or improvement of a series of fundamental physical, chemical, and formulation properties of a drug before designing a formulation prescription to make the drug stable, effective, and in line with the requirements of formulation prescription and formulation process in industrial production. Medicilon can provide professional pre-prescribing services and uncover valuable information to lead the compound into late-stage development for tiny quantities of active pharmaceutical ingredients or candidate compounds with drug-forming properties.

The impact of physical properties of active pharmaceutical ingredients (APIs) on pre-prescription studies of injectables is one of the main points of pre-prescription studies of injectables, which are mainly reflected.

1. Like formulations, pre-prescription studies of injectables should fully understand the physical properties of APIs

Pre-prescription studies of injectables and formulations alike must fully understand the study of the physical and chemical properties of the API. For injectable products, in-depth API research has three purposes.

(1) To help obtain the critical physicochemical properties related to dosage form design.

(2) To help guide the modification of molecules (e.g., into salts, etc.).

(3) To help develop stable and commercially viable products.

Research on excipients is aimed at achieving a rational selection of the type and amount of excipients and avoiding their misuse. The fewer excipients for injectables, the safer the injectables will be. For packaging materials, a better understanding is needed to aid product design, stability, and patient compliance.

The study of the physical properties of APIs is a game; whether to spend more time studying the physical properties of injectable APIs is a question that needs to be thought about; the physical properties of the study are not deep enough, sometimes the impact on injectables is often more significant than oral formulations, the effect is also more profound.

2, API solid crystalline research on the impact of injectables

According to the physical nature of the division, the standard API can be divided into a crystalline, liquid crystal, and non-crystalline. The injectable may be more helpful for the study's above-mentioned physical properties than solid oral formulations. For example, suppose an API is polycrystalline, then for injectables. 

In that case, the most thermodynamically stable reliable drug has the most negligible solubility, and usually, the best stability is given priority for generic drug development. The question arises, what if the solubility of a solid API does not meet the requirements to become an injectable? If the crystalline form has not been thoroughly studied, it may get into trouble; and if several crystalline forms of API have been reviewed, then a sub-stable form can be used instead.

In the case of the solvent compound and hydrate APIs, although the stability of solvent compounds/hydrates and substances in a given solvent or water is generally good, the solubility is generally not high. Usually, the non-hydrates are chosen for development. If the hydrate is the only crystal form or has better properties, we will pick it, but the subsequent development work may also be more difficult. Due to the ability of water molecules to have multi-directional hydrogen bonds, organic compounds are often hydrates, and research and development should be done with care.

An amorphous compound has a higher free energy than a crystal because it does not have long and ordered molecules, so it is less chemically stable. 

Due to thermodynamics, it will spontaneously change to a more chemically stable form, and correspondingly, its physical stability is poor. Special attention is paid to the fact that when the developed product is an amorphous compound, after administration, it may change to a more stable crystalline form in the human body, leading to a decrease in solubility, which in turn affects the release of the drug, thus leading to a failure to meet the efficacy targets. Therefore, it is necessary to conduct adequate research on the crystalline form for injectables.

3, The effect of API powder characteristics on injectables

There are some injectables, such as lyophilized powder injection, whose API is a powder; for powder, we usually need to pay attention to its liquidity because if the liquidity is not good, it may lead to the instability of the product composition. For example, when the powder falls to the bottom of the bottle, it will form some "holes" because the force between the particles is too large, and the homogeneity of the product may be challenging to ensure. 

Mobility is a critical value that characterizes the beginning of the movement of the powder. When doing the screening and process, the powdered API may vary in density, humidity, and other factors. Therefore, flowability can be used as a measure when screening different prescriptions. If the flowability is good, adding other excipients may not be necessary. The research of some seemingly unimportant physical properties can often play a more positive role in prescription research and screening, and the more experimental accumulation and data accumulation, the more positive effect it can have on prescription screening.

Chinese pharmaceutical preparations include ancient tonics, medicinal wines, quats, pills, pans, creams, and pans, and many proprietary Chinese medicines already available. Since the second half of the 19th century, the formulation industry has developed into a separate field in drug production, with the development of many new formulations such as tablets, sugar-coated tablets, enteric-coated tablets, film-coated tablets, injectables, capsules, suppositories, aerosols, pharmaceutical films, as well as a variety of extended-release and controlled-release formulations. 

Medicilon provides one-stop and systematic formulation development services covering both innovative and generic drugs to meet customers' needs at different stages of development and is committed to providing contract R&D services in solid formulations, semi-solid formulations, liquid formulations, and innovative formulations, etc. Process studies can be conducted according to the characteristics of the dosage form, taking into account the drug's physical and chemical properties and stability and considering the production conditions and equipment. Initially, determine the preparation process of laboratory samples and establish the corresponding process control indexes.