Methods of screening for possible solid forms

Chemistry: analytical and immunological testing – Including sample preparation – Gaseous sample or with change of physical state

Reexamination Certificate

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

C436S174000, C436S180000

Reexamination Certificate

active

06750064

ABSTRACT:

FIELD OF THE INVENTION
The present methods relate to screening for possible solid forms of a sample and include solidifying the sample in at least on receptacle defining a capillary space, such as a capillary tube of well plate. The present methods also relate to screening a sample according to its solid forms and include solidifying the sample in a plurality of receptables and at least one receptacle defines a capillary space. The solid for of the sample refers to its arrangement at the molecular or atomic level in the solid. The solid forms generated by the solidification step are analyzed and classified, such as by x-ray diffraction patterns. The present methods increase the likelihood of generating all or a high percentage of possible solid forms.
BACKGROUND OF THE INVENTION
In the chemical field, the unpredictability and variability of compounds, mixtures, and processes are well established. Certain chemical compounds or mixtures may have utility for numerous different applications, including vital biological applications, yet a slight change in those compounds or mixtures, even with respect to a single atom, may reduce or eliminate their utility for their beneficial purpose. Similarly, certain chemical processes may have significantly better or worse performance based upon seemingly minor differences.
In the pharmaceutical field, a great deal of time, effort and expense is spent on the identification of particular compounds and mixtures that will have beneficial effect. Furthermore, exhaustive research must be done as to whether such compounds and mixtures will have harmful effects. Once again, even slight differences in chemical composition or structure may yield significant differences in biological activity. Thus, researchers frequently test many different compounds and mixtures for biological activity and other effects as well as testing different processes and conditions for the preparation of such chemical compounds and mixtures.
The process of thorough analysis of different chemical compounds, elements, mixtures, processes, or structures is commonly referred to as screening. Screening may be a function of time and effort, with the quality or results of screening being a function of the number of samples prepared and/or analyzed as well as the quality of preparation and/or analysis underlying those samples. Screening plays a vital role in the pharmaceutical field, as the most advantageous formulation of a biologically active compound or mixture is frequently found through successful screening processes.
However, screening processes can require significant amounts of time, effort and resources. There is a continuous need for improved screening processes having increased reliability and efficiency.
Processes have been used for screening chemical compounds according to their form. When a compound has different solid or crystalline forms, the different forms are frequently referred to as polymorphs of the compound. A “polymorphic” compound as used herein means a compound having more than one solid form. For example, a polymorphic compound may have different forms of its crystalline structure, or different forms based upon hydration, or it may have a crystalline form and an amorphous form. In the past, screening processes have not identified with sufficient consistency and reliability a high percentage of possible solid and semisolid forms.
The form of a compound or mixture may have an impact on biological activity. The same chemical compound may exhibit different properties depending upon which form (such as amorphous or crystalline or semisolid) that compound is in. A “semisolid” form is used herein to indicate materials like waxes, suspensions, gels, creams, and ointments. The term “solid form” herein includes semisolid forms. Furthermore, a chemical compound may exist in different solid forms, and those different solid forms may also exhibit different properties. As a result, different solid forms, including different crystalline forms, of a chemical compound may have greater or lesser efficacy for a particular application. The identification of an optimal solid form is important in the pharmaceutical field, as well as in other fields including nutraceuticals, agricultural chemicals, dyes, explosives, polymer additives, lubricant additives, photographic chemicals, and structural and electronic materials. The new methods described herein may be useful in any of these fields as well as others where solid materials are used.
A chemical compound or mixture may be amorphous, meaning that it is not characterized by a regular arrangement of molecules. Alternatively (or even to a limited extent within a mostly amorphous form), a compound or mixture may be arranged in a crystalline state, where the molecules exist in fixed conformations and are arranged in a regular way. The same compound or mixture may exhibit different properties depending upon which solid form that compound or mixture is in.
It is important in the pharmaceutical field as well as other fields to find the form of a chemical compound that exhibits appropriate physical and chemical properties. One form may be more stable or have other properties that make it preferable over other forms. One form of a chemical composition may have better bioavailabilty, solubility, or adsorption characteristics or in other ways be more suitable for delivery of therapeutic doses than other forms. As part of a screening method, it may be advisable to evaluate different salts of a chemical compound (or more precisely, different salt compounds of a given biologically active ion). It is frequently desirable within a screening process to generate, or at least search for, a high percentage of the possible solid forms of a compound or mixture. Past attempts to generate a variety of solid forms involved flash evaporations, cooling under different conditions and/or the addition of seeds of solid material. However, some materials strongly resist the generation of new solid forms.
One or more solid forms may be generated by crystallization of the sample. Among the phenomena in crystallization are nucleation and growth. Crystal nucleation is the formation of an ordered solid phase from liquids, supersaturated solutions, saturated vapors, or amorphous phases.
Nucleation may be achieved by homogeneous or heterogeneous mechanisms. In heterogeneous mechanisms, some solid particle is present to provide a catalytic effect and reduce the energy barrier to formation of a new phase. Crystals may originate on a minute trace of a foreign substance (either impurities or container walls) acting as a nucleation site. Since nucleation may set the character of the crystallization process, the identity of the foreign substance is an important parameter. The presence of “seeds” of other crystalline compounds in a crystallization environment can be beneficial, detrimental, or both, but in any event, must be considered. Growth is the enlargement of crystals caused by deposition of molecules on an existing surface. In homogeneous mechanisms, it has been theorized by others that nucleation is achieved spontaneously with the solution comprising the solute to be crystallized in solvent typically by evaporation, temperature reduction, or addition of antisolvent.
Typically, a solid to be crystallized is present in a solution at, above, or below its saturation point at a given temperature. Crystallization is initiated or facilitated by removing solvent, changing temperature, and/or adding an antisolvent. The solvent may be removed by evaporation or other means. Eventually the solution reaches a point where crystals will grow.
A specific chemical substance may crystallize into different forms or transition from one polymorph form, pseudopolymorph form, or amorphous form to another form. This crystallization into a different form or transition into a different form may be accompanied by other physical or chemical changes. For example, novobiocin has at least two different forms: an amorphous form and a crystalline form. Dog plasma levels of novobiocin vary depending

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Methods of screening for possible solid forms does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Methods of screening for possible solid forms, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods of screening for possible solid forms will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-3366168

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.