Granulation is an exemplary of particle design and the properties of the particles acquired after granulation depend on particle size of the drug and excipients, the type, concentration, and volume of binder and/or solvents, granulation time, type of granulator, drying rate (temperature and time), etc. The primary methods by which the agglomerated granules are formed include solid bridges, sintering, chemical reaction, crystallization and deposition of colloidal particles.1,3 Besides, binding can also be accomplished through adhesive and cohesive forces by utilizing high viscous binders. The series of mechanisms by which granules are formed from the powder particles encompass wetting and nucleation, coalescence or growth, consolidation, and attrition or breakage.3-5
pharmaceutics the science of dosage form design pdf download
The technical effects resulting from the differences were that the claimed composition was stable and it possessed excellent dissolution and bioavailability properties. The objective technical problem to be solved was to provide a stable dosage form of nilotinib which possesses excellent dissolution and bioavailability properties. In view of the BCS Class of nilotinib, the skilled person would have been motivated to provide a liquid formulation and in view of the hygroscopicity, the skilled person would have sought a soft gelatin capsule formulation over a hard capsule. The only example of a dosage form in the closest prior art D3 was a soft capsule in Example 97, in which the active ingredient is suspended in liquid. The general teaching of D3 is that liquid compositions were preferred. Thus, claim 1 was inventive because the skilled person would not have sought to solve the problem by providing nilotinib in the form of granules.
With regard to the physical stability of the dosage form, paragraph [0050] of the patent mentions that "because of the slight hygroscopic tendency of the nilotinib hydrochloride monohydrate, it may be expected that the filled hard gelatin capsule shells would deform over aging" but that "surprisingly, the physical stability of the filled hard gelatin capsules did not substantially deform during visual inspection during accelerated aging". The passage of paragraph [0050] further point out that "preferably, in order to achieve this stability, the water content of the capsules should so low that upon drying the capsules for 10 min at 80 C the loss of weight should be lower than 3.0 %", an optional feature not present in claim 1 of .
Accordingly, the physical stability has been achieved with the use of the hard capsule, which is also the type of dosage form disclosed in document D3 on page 34. Accordingly, it is not possible to conclude to an improvement of the physical stability over the closest prior art.
D7 is a common general knowledge document on pharmaceutical excipients and the cited passages relate to silicon dioxide, lactose, magnesium stearate, poloxamer, and povidone, as well as their possible use in pharmaceutical dosage forms.
However, the Board notes that D3 discloses a capsule comprising a granulate only as a possible option among numerous other alternatives. Even if it may be understood from D3 that the compounds of formula I present solubility issues, the teaching of D3 directs the skilled person rather to a formulation in liquid form, since it is explicitly disclosed that "preference is given to the use of solutions of the active ingredient, and also suspensions or dispersions" (see D3, page 33, 5th paragraph). Furthermore, D3 does not provide any pointer to use a surfactant in solid dosage forms, let alone poloxamers. In particular, there is no teaching neither in D3 nor in any other cited document that poloxamer would provide the best dissolution profile for the poorly soluble nilotinib, as shown in D37. There is also no clear indication in D3 as to whether the excipients should be included in the granules or mixed with them. The generic statement on page 34 does not specify this.
The Board considers however that at least steps (ii)-(iv) involve choices which have to be made within several possibilities. This results in the start of a screening and research program which implies that several decisions are to be taken among different existing effective ways to improve the solubility (e.g. changing the dosage form to a solubilised form, adding excipients such as polymers, altering the pH, adding co-solvents, etc.), then possibly among several different effective compounds that can be used to improve the solubility (e.g polymers such as shown in D37, etc.), then finally among several possible surfactants (e.g sodium lauryl sulfate, as also shown in D37, etc.). Hence, arriving at the claimed solution cannot be made without hindsight knowledge of the invention.
The Master of Science in pharmaceutical sciences degree is designed to prepare an individual for responsibilities in professional practice, the pharmaceutical industry and scientific research beyond those possible with a baccalaureate degree.
The Industrial Pharmacy program at The University of Toledo prepares students to assume pharmaceutical manufacturing positions performing a variety of specialized tasks including pre-formulation evaluation, dosage form design, and stability testing. Graduates of the program go on to prestigious PhD programs throughout the United States as well as entry-level scientist positions in the pharmaceutical industry across the world.
Pharmaceutics is the discipline of pharmacy that deals with the process of turning a new chemical entity (NCE) or old drugs into a medication to be used safely and effectively by patients. It is also called the science of dosage form design. There are many chemicals with pharmacological properties, but need special measures to help them achieve therapeutically relevant amounts at their sites of action. Pharmaceutics helps relate the formulation of drugs to their delivery and disposition in the body.[1]Pharmaceutics deals with the formulation of a pure drug substance into a dosage form.Branches of pharmaceutics include:
Pure drug substances are usually white crystalline or amorphous powders. Before the advent of medicine as a science, it was common for pharmacists to dispense drugs as is. Most drugs today are administered as parts of a dosage form. The clinical performance of drugs depends on their form of presentation to the patient.[2]
Duloxetine hydrochloride is an antidepressant drug also approved for diabetic neuropathy, anxiety disorders, and fibromyalgia requiring repeated administration on chronic basis. The objective of this study was to develop a transdermal drug delivery system for duloxetine hydrochloride as a once daily dosage form.
Transdermal drug delivery systems (TDDSs) can be defined as self-contained discrete dosage forms which, when applied to the intact skin, deliver the drug(s) through the skin portal at a predetermined and reproducible rate into the systemic circulation over a prolonged period of time (Prabhakar et al. 2013; Prausnitz et al. 2004; Gupta et al. 2009). The goal of dosage design for transdermal products is to maximize the flux through the skin into the systemic circulation and simultaneously minimize the retention and metabolism of the drug in the skin. Transdermal delivery provides a leading edge over injectables and oral routes by increasing patient compliance and avoiding first pass metabolism, respectively (Selvam et al. 2010).
Pharmaceutics is a multidisciplinary science that focuses on the study of the physical, chemical and biological properties of drugs and dosage forms. Cutting across the traditional disciplinary boundaries, pharmaceutics examines the relationship of drug properties to dosage form design, fabrication, evaluation and therapeutic efficacy. Students in the Ph.D. program's Pharmaceutics Concentration may develop research programs in the areas of drug delivery systems, drug stability, dosage forms, pharmacokinetics and drug discovery.
Recently, controlled release (CR) pharmaceutical products have become a very useful tool in medical practice, offering a wide range of actual and perceived advantages to the patient. A CR product requires numerous considerations, like drugs suitable for CR formulations, techniques of fabrication and evaluation, factors affecting bioavailability of the parent drug, before it can actually be claimed to provide the purported benefits. Such complex considerations fall under the domain of pharmaceutical experts and clinicians, naturally, are not sufficiently aware and updated about these products and their biological consequences. Various CR formulations used in neurological practice are discussed in the present review. The clinical studies of the conventional and CR dosage form of the drugs used in neurology practice reflect the advantages of prescribing CR formulations over the conventional dosage forms.
Hydatid disease occurs in most areas of the world and currently affects about one million people. Albendazole is an orally administered broad spectrum anthelmintic drug approved by US FDA in 1996. Literature review suggests Albendazole is low solubility compound and most of the studies were performed to improve the solubility with traditional approach of product development. The present study was aimed to apply Design of Experiments (DoE) in the development and optimization of drug release from new Albendazole tablets using three factor two level (23) full factorial designs with integrated Quality be Design (QbD) approach. New Albendazole tablets were formulated using micronized grade of the Albendazole active and excipients were selected inline with market reference product. Quality target product profile (QTPP) and Critical quality attributes (CQAs) were designed. Risk assessment was used to identify the Formulation variables impacting CQA dissolution. The amount of Formulation variables were optimized on the basis of drug release profiles at 15 minutes and 30 minutes of different formulation batches manufactured based on 23 full factorial design. Tablets were prepared by wet granulation technique and evaluated for various physicochemical parameters and in vitro drug release. Formulation trials dissolution results at 15 minutes and 30 minutes were evaluated to derive the concentration of Formulation variables which will achieve the release of more than 80%. Analysis of variance (ANOVA) analysis, Pareto chart and Contour plot were used to predict the values of formulation variables and their effect on dissolution. Updated risk assessment of the Formulation Variables was performed and justification was provided for reduction of risk from medium to low level. Optimized formulation from DOE had comparable dissolution profile with market reference tablet. Stability studies of new Albendazole tablets 200 mg were conducted at ICH accelerated conditions and found to be stable. Thus studies revealed that full factorial experimental design could efficiently be applied for optimization of formulation variables affecting drug release. New Albendazole tablets 200 mg successfully formulated with application of the integrated quality by design (QbD) and design of experiment (DOE) approach and thereby achieved comparable release profile with market reference product. 2ff7e9595c
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