Preformulation Analysis

The major distinction in the internal structure of a drug substances is that the solid is crystalline or amorphous. Given the fact that the crystal habit and internal structure of a drug substances has a significant role in affecting the materials' physicochemical properties such as flow-ability and stability. Importantly, for most of crystalline substances, certain amounts of amorphous (non-diffracting) components are contained. In this case, identification and quantitation of the crystallinity or amorphous content are critical to manufacture's drug development. Alfa Chemistry is capable of conducting screening of polymorphic forms for many kinds of drug substances and inactive ingredients by utilizing a series of techniques such as DSC, XRPD and FTIR. With in-depth knowledge and extensive expertise for performing exhaustive materials screening for our clients in worldwide, our scientists have enough capacity to provide solutions for addressing your specific problems and offer the solid state characterization services to meet your scale-up needs.

Drug hygroscopicity represents the capacity of a solid drug substance to absorb surrounded moisture. Certain important parameters (such as chemical stability, flow ability and compatibility) of high hygroscopicity drugs can be significantly influenced by the changes of moisture level. In this case, the investigation of hygroscopicity of compounds plays a critical role in the determination of drug storage conditions. Through a suit of methods and analysis techniques, we are capable of providing you comprehensive hygroscopicity testing for supporting your drug development. Our analysists have decades of experiences in offering customized testing and researching services for our global clients. With a variety of advanced instrumentation, our experts will work with you to analyze the materials' or product's hygroscopicity comprehensively and finally provide you a useful report for your further strategy development.

The moisture/ solvent content of tablets determines the release of their active ingredients as well as their chemical, physical, microbial and shelf-life properties. Accordingly, the moisture/ solvent content is of crucial importance and has to be accurately determined. To meet your requirements for efficient and accurate determination of moisture content in drug substances or end pharmaceutical products, techniques such as loss on drying (LOD), karl fischer titration and capacitance and radio frequency are available in our analysis department. For solvent content analysis, the typical headspace gas chromatography (GC) and mass spectrometry (GC-MS) will work together for identification and quantification of your solvent analysis. With knowing the significant adverse effect of moisture/ Solvent content on your products and the supply chain, our experts who are experienced in performing various analysis can provide you a full range of testing services.

Physical properties of active ingredients and excipients including particle size, shape and surface area are the important characteristic for materials used to fabricate pharmaceutical formulations. The size of particles, distribution and the shape, for example, have significant effect on the product performance, processability, stability and appearance of the final products. Besides, fine materials, compared with the coarse materials, are easier to be attacked by atmospheric oxygen, the humidity, and interacting excipient. The linkage between surface area of active ingredients and the performance of drug formulation is also well documented. In this case, proper matching of particles size, shape and surface area for API and excipient are of great importance to drug development. Alfa Chemistry can provide both the analytical tools and technical support to help our customers to characterize their particulate systems that are favorable to formulate and manufacture many pharmaceutical dosage forms. Through a variety of advanced analytical techniques such as high performance laser diffraction analyzer, nanopartica series instruments, dynamic image analysis system and BET flowing gas surface area analyzers, experts from our laboratory are able to conduct a comprehensive particle size analysis. For surface area investigation, the equipped BET techniques include Micromeritics TriStar (N2 and Kr), Micromeritics Gemini V and VII models can be accessible to our analysts for supporting your needs.

Understanding of the mechanical properties of pharmaceutical powders can predict the comminution and compaction behavior of a material during tablet preparation. To support your drug development, a comprehensive investigation of mechanical properties of drugs and excipients will be performed at Alfa Chemistry through methods such as Young's Modulus, hardness analysis and surface energy testing. Importantly, we guarantee that your mechanical properties analysis will be performed by our most experienced work team who is dedicated to providing test and research service in pharmaceutical industry. Our excellent scientists are able to handle a wide-range of mechanical properties testing services with high efficacy and accuracy. With offering valuable insight about your development strategy, we are confident to assist you in promoting your product's rapid development and final listing.

An excellent shear stability of materials and end products is critical to maintaining the consistency of the physicochemical properties, quality and component proportion. With an efficient workflow and a variety of state-of-the-art techniques, our well-trained analysists are capable of offering you a suitable analytical procedure and an accurate investigation report. For supporting your product's development, our experts will work with you to develop an appropriate solution to address any unresolved problems. Based on the principle of bringing quality and safety to life, Alfa Chemistry will provide a total quality assurance expertise for ensuring your product to meet and even exceed quality, safety and regulatory standards.

Suitable vehicles are extremely critical to the intrinsic properties of drug formulation such as API's release, absorption, distribution and (local) tolerance. Therefore, an ideal vehicle for drug substances testing during preformulation exact negligible impact on any biological activity of active ingredients and has no risk of inducing any toxicity that would mask or confound the effects of the API of interest. At Alfa Chemistry , suitable vehicles are selected according to their functionality, compatibility, and variability of critical material attributes. Additionally, various sophisticated screening techniques and analysis platforms in our laboratory make your vehicle selection performed more efficiently and accurately. With the high-quality team form our departments, we are capable of offering a comprehensive data report for your supporting your drug development.

Chirality/Enantiomeric forms of a drug can differ in potency, physicochemical properties, and behavior in biological systems. During preformulation, a suitable chirality or enantiomeric form will be identified and separated by our experienced team using various advanced techniques and methods. To meet your requirements for separation of chirality/enantiomer drug substances, your chemical molecules will be subjected to rapidly screening through our Chiral Stationary Phases in HPLC or SFC modes. Post identification of an appropriate analysis method, the enantioseparation of your racemic mixture is able to be done within short days (not more than 10 days) with the purified enantiomers, which can match the specifications of > 98% enantiomeric excess and > 85% yield. For satisfying your different separation requirements, varying scales of chirality/enantiomer drug separation can be offered as follows:

Small Scale Separation: Small-scale separation is designed to offer our clients a rapid access to pure chirality/enantiomers. The quantities of samples during this kind of analysis can be ranged from a few milligrams to tens of grams.

Medium Scale Separation: During such scale of separation, the best protocol for separating your racemic mixture will be established by our advanced Chiral Technologies. Besides, the HPLC and SFC modes involved method development strategy can determine the production rate and ensure complete recovery of the purified enantiomers.

Large Scale Separation: Together with our preparative equipment global capabilities and batch HPLC or SMB systems, experienced scientists from Alfa Chemistry can provide the best separation method for your large-scale projects.

Recognizing the fact that the majority of drug candidates have bioavailability challenges and even fail in phase I-III clinical trials due to their poor solubility. In this case, solubility or equilibrium solubility of drug substances represent a critical and extensively studied parameter for preformulation investigation. A comprehensive determination of drug solubility enables an optimal selection of solvent medium for a drug to be achieved and can overcome certain challenges in drug formulation development. At Alfa Chemistry , solubility of the molecules in various solvents and enhanced solubility by surfactants, complexation agents or salts will be comprehensively determined for the next step of formulation preparation. Besides, a broad suite of technique platforms and analytical methods have been established in our laboratory to support addressing certain complex solubility challenges. Our experts have extensive experience in providing formulation services for our customers and are professional in optimization of your drug products for improving your product's bioavailability.

Lipophilicity (logP and logD), pKa and pH solubility are the inherent properties of drug substances and inactive components that have an essential effect on the end product's physicochemical properties, quality and potency. Comprehensive assessment of these physicochemimal properties for drug compounds is thought to be pivotal in the early stages in drug development. Taking the solubility for example, a drug candidate that has a favorable Hydrophile-lipophile balance (HLB) can not only permeate across biological membranes such as the intestine wall, but also dissolve to blood/plasma and other aqueous bodily fluids. At Alfa Chemistry , we can apply the UPLC-UV and MS quantitation or other techniques to help you with determination of the compound's division between water and octanol phases. Additionally, solubility analysis will be investigated in PBS at various pH values. pKa testing will be performed by our analysists through calculating the logS or logD values and measuring in various pH values (ranging from pH 2 to pH 10). Our experts are professional in testing the physicochemical properties of various compounds and will provide you a full reporting of the characterization on our website or through email.

In the stage of preformulation, there is a critical role for stability testing from which you can obtained useful information on how environmental factors such as temperature, humidity and light influence the quality of drug products. Based on the generated data during stability testing, we can determine a retest period for a drug substance to predict a recommend storage condition and a shelf life for your final drug formulation. The stability study in our laboratory will be performed under the fully validated, controlled and monitored conditions and the ICH guidelines. With on-site cGMP stability storage at ICH conditions, our experts will manage your preformulation stability programmes including solid-state stability testing, solution-state stability testing and drug-excipients compatibility studies. Additionally, at Alfa Chemistry , you can get the world-class expertise and resources to support your testing need for the stability investigation of your pharmaceutical or biologic projects. With decades of experiences and great storage capacity, the life science laboratories form Alfa Chemistry are able to handle your stability projects under the fully validated, controlled and monitored conditions and the ICH guidelines. 

Pharmacokinetic evaluation acts as a key activity in the stage of early drug development. With a profound understanding of your product's PK, dosage regimens can be subsequently well designed and adjusted by drug-drug interactions and special patient groups. Based on this, the pharmacokinetic properties (PK) of a test article should be regarded as one of the essential components of drug discovery and development programs.The PK evaluation services at Alfa Chemistry can be exploratory and extensive and we provide pharmacokinetic evaluation services including but not limited to studying compounds in various formulations, evaluating the metabolism of analogs in vitro and in vivo, dose escalation studies in rats or dogs, metabolic kinetics with active metabolites and drug distribution in tissue/organ and body fluid. Accessible to many kinds of state-of-the-art analytical platforms and methods LC-MS/MS – Alfa Chemistry SCIEX 5500 and robotic sample prep systems, we can provide a quick turnaround PK screening for your strategy optimization or formulation evaluation.

As an important phase in the preformulation stage, drug-excipient compatibility investigation is provided to analyze the potential physical and chemical interactions between API and inactive compounds. The interactions between excipients and drug substances are supposed to play an important role in the physicochemical properties, therapeutical effects and the stability of the final dosage form. Therefore, elaborate evaluations of the potential of different excipients should be taken into a significant strategy position especially for the oral solid dosage forms which require many excipients to provide the desired features for its formulation. For excipient compatibility testing, scientists from Alfa Chemistry can provide you with three types of incompatibility assays including physical incompatibility, chemical incompatibility and therapeutic incompatibility evaluation. The advanced analytical technique platforms can be utilized to determine drug-excipient compatibility in our laboratory including differential scanning calorimetry (DSC), isothermal microcalorimetry, hot stage microscopy (HSM), scanning electron microscopy (SEM) and other chromatography such as thin layer chromatography (TLC), high-performance liquid chromatography (HPLC) and self-interactive chromatography (SIC).