"The Encyclopedia of Pharmaceutical Technology presents up-to-date and interdisciplinary contributions by leading international authorities in all areas of drugs. Presenting authoritative and engaging articles on all aspects of drug development, dosage, manufacturing, and regulation, this Third Edition enables the. Encyclopedia of Pharmaceutical Technology, Second Edition - Three Volume Set James Swarbrick No preview available -
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Encyclopedia of. PHARMACEUTICAL. TECHNOLOGY. Third Edition. VOLUME 1. New York London edited by. James Swarbrick. Get this from a library! Encyclopedia of pharmaceutical technology. Volume 1. [ James Swarbrick;]. Encyclopedia of Pharmaceutical Technology, Volume 20 - Ebook download as PDF File .pdf), Text File .txt) or read book online.
Doshi Burgess Woznicki and David R. Schoneker Compendial Specifications Lee T. Grady Rippie Computer-Aided Drug Design J. Phillip Bowen and Michael Cory Computers in Pharmaceutical Technology Onkaram Basavapathruni Contamination Control Richard G. Johnson Chien Cooling Processes and Congealing James W. McGinity and Mark D.
Coffin Coprecipitates and Melts Madhu K. Vadnere Corrosion in Pharmaceutical Processing Arvind N. Narurkar and Pai-Chang Sheen Rieger Cosolvents and Cosolvency Joseph T. Rubino Flynn Design of Drugs: Basic Concepts and Applications Jacques H. Poupaert 1.
Diffuse Reflectance Spectroscopy Michael Bornstein Direct Compression Tabletting Ralph F. Dissolution and Dissolution Testing James L. Ford Howard, and John W. Mauger Dosage Form Design: A Physicochemical Approach Michael B.
Maurin, Anwar A. Hussain, and Lewis W. Dittert Dosage Forms: Non-Parenteral Paul Zanowiak Parenteral Salvatore J. Turco Dosing of Drugs: Cook and Aziz Karim Dressings in Wound Management Terence D.
Turner Wong, and Su Il Yum Drug Information Systems John M. Fischer Rapp Drug Safety Evaluation Farrel L. Groves and Michael J.
Groves Drying and Driers Kurt G. Van Scoik, Michael A. Zoglio, and Jens T. Cocks 1. Elastomeric Parenteral Closures Kenneth E. Avis and Edward J. Electrochemical Methods of Analysis Barbara J. Norris Electron Beam Sterilization Marshall R. Cleland and Jeffrey A. Beck Enteric Coatings Walter G. Chambliss Enzyme Immunoassay Hsin-Hsiung Tai Equipment Selection and Evaluation Bhoghi B.
Sheth and Fred J. Bandelin Ethics of Drug Making Michael Montagne Ethylene Oxide Sterilization Robert R. Reich and Daniel J. Evaporation and Evaporators David P.
Extrusion and Extruders K. Fielden and J. Newton Fermentation Processes Peter F. Stanbury Film Coatings and Film-Forming Materials: Evaluation Galen W. Radebaugh 1. Films and Sheets for Packaging Shalaby W. Shalaby and Bernard L. Williams Filters and Filtration Theodore H. Meltzer Flavors and Flavor Modifiers Akwete L. Adjei, Richard Doyle, and Thomas Reiland Flow Properties of Solids Stephen A.
Howard and Jin-Wang Lai Mathur Food and Drug Administration: Role in Drug Regulation James C. Morrison DerMarderosian Gamma Radiation Sterilization Geoffrey P. Jacobs Gastrointestinal Absorption of Drugs Alice E.
Loper and Colin R. Gardner Kibbe and Lawrence C. Weaver Clark Glass as a Packaging Material for Pharmaceuticals R. Hirsch Good Manufacturing Practices: Halohydrocarbons, Pharmaceutical Uses Richard N. Dalby Health Care Systems: The United States Henri R. Manasse, Jr. Outside the United States Albert I. Wertheimer and Joaquima Serradell Markovitz Sutter High-Performance Liquid Chromatography R.
Raghavan and Jose C. Joseph Buerki and Gregory J Higby Home Parenteral Therapy Hetty A. Lima Homogenization and Homogenizers Graham C.
Cole Hydrolysis of Drugs Kenneth A. Connors 1. Immunoassay H. Thomas Karnes, Mohamadi A. Sarkar, Guenther Hochhaus, and Stephen G. Schulman Implants and Implantation Therapy Hitesh R. Bhagat and Robert S. Langer Infrared Spectroscopy Shuyen L. Huang Intranasal Drug Delivery Kenneth S. Su Borodkin Irrigation Solutions Steven B. Moody Laminar Airflow Equipment: Lens Care Products Kiran J.
Randeri, Ronald P. Quintana, and Masood Chowhan McMann Weiner Crommelin 1. Liquid Oral Preparations Jagdish Parasrampuria Management of Drug Development Donald C. Monkhouse, Ralph A. Blackmer, and Wendy A. Valinski Manufacture of Pharmaceuticals John C. Griffin Marketing of Pharmaceuticals Mickey C. Mass Transfer in Unit Operations J.
Bourne Metered-Dose Inhalers: Nonpressurized Systems Paul J. Atkins Pressurized Systems Gerald W. Hallworth Microbial Control of Pharmaceuticals Nigel A. Halls Microsphere Technology and Applications Diane J. Burgess and Anthony J. Hickey 1. Moisture in Pharmaceutical Products R. Gary Hollenbeck Cannon, Pramod K. Gupta, and Ho-Wah Hui Mouthwashes and Periodontal Disease Daniel A.
Mucosal Adhesive Preparations Kalpana R. Kamath and Kinam Park Nasal Drug Delivery: Trends and Perspectives Frans W. Merkus and J.
New Drug Applications Dhiren N. Shah and Sidney Goldstein Gibson and H. Donald Burns Bernstein Nuclear Medicine and Pharmacy Richard J.
Kowalsky and Alan F. Parr 1. Desai and James Blanchard Doornbos and Pieter de Haan Orphan Drugs Carolyn H. Large Volume Salvatore J. Small Volume Michael J. Akers Patents in the Pharmaceutical Industry Stuart R. Suter Wearley and Ajay K. Banga Permeation Enhancement through Skin Adrian C. Williams and Brian W. Barry Pharmaceutical Packaging Donald C.
Liebe 1. Pharmacokinetics and Pharmacodynamics John J. Pharmacopeial Standards: Artiges Japanese Pharmacopeia Mitsuru Uchiyama United States Pharmacopeia Jerome A. Halperin and Lee T. Photodecomposition of Drugs John V. Greenhill Wilson Pilot Plant Design Robert M. Franz, Robert D. Copeland, Lawrence D. Lewis, and William C.
Stagner Pilot Plant Operation Leonard A. Amico, Ralph B. Caricofe, James D. English, Gary W. Goodson, Lawrence D. Lewis, and Robert M. Franz Plant Products as Drugs D. Lewis Polarography and Voltammetry A. David Woolfson Medicinal and Pharmaceutical Julian H. Braybook Post-Marketing Surveillance Win M. Castle and Suzanne F. Cook Prescribing of Drugs Michael C. Gerald Preservation of Pharmaceutical Products Sally F.
Bloomfield and Fiona C. Sheppard 1. Preservative Testing Norman A. Hodges and Stephen P. Denyer Shah and James G. Kenimer McGilveray Pyrogens and Pyrogen Testing Marlys E. Weary Radiation Sterilization of Drugs Stephen G. Schulman and Phillip M. Achey Receptors for Drugs Jeffrey M. Herz, William J. Thomsen, Richard Mitchell, and George G.
Fix and J. Howard Rytting Registration of Drugs William J. Currie and Richard W. Currie Rheology of Pharmaceutical Systems Brian Warburton Robotics in the Pharmaceutical and Biomedical Laboratory J. Wieling Bighley, Stephen M. Berge, and Donald C. Monkhouse Semisolid Preparations Fred J. Bandelin and Bhogi B. Sheth Sieving of Pharmaceuticals John W. Mullin Li Spheronization J. Killeen Starches and Starch Derivatives Ann W.
Newman, Imre M. Vitez, Chris Kiesnowski, and Ronald L. Mueller Corrigan and Anne Marie Healy Popp Tooling for Pharmaceutical Processes Dale Natoli Sams Walters Unit Processes in Pharmacy: Fundamentals David Ganderton and Anthony J. Hickey Bowersock and Kinam Park Validation of Pharmaceutical Processes Robert A. Nash Veterinary Uses of Drugs Joy B. Reighard Water for Pharmaceutical Use Rostyslaw O. Slabicky Kontny Isolators for Pharmaceutical Applications Gordon J. Farquharson Solubilization of Drugs Paul B.
Myrdal and Samuel H. Yalkowsky Tablet Compression: Bogda Targeting of Drugs to the Gut I. Wilding and S. Davis Transdermal Drug Delivery Devices: System Design and Composition George A. Patani and Yie W. Ultrasonic Nebulizers Orla N. McCallion and Kevin M. Taylor Blood Substitutes: Nelson 1. Contract Manufacturing Duncan E.
McVean Olson Brendel, and Richard J. Washkuhn Rowe and Ronald J. Roberts Hot-Melt Extrusion Technology J.
Encyclopedia of pharmaceutical technology. Volume 1
McGinity, J. Koleng, M. Repka, and F. Zhang Cocchetto and Sherman N. Alfors Peters and Marghi R. McKeon Schmidt Morisseau and Christopher T. Rhodes Blow-Fill-Seal BFS technology was developed in the early s and was initially used for filling many liquid product categories, for example, nonsterile medical de- vices, foods, and cosmetics.
The technology has been developed to an extent that today BFS systems are used to aseptically produce sterile pharmaceutical products such as respiratory solutions, ophthalmics, and wound-care products throughout the world. The BFS technology is an advanced aseptic processing technique which allows plastic containers to be formed by means of molded extruded polymer granules, filled, and sealed in one continuous process.
This differs from conventional aseptic pro- cessing where container formation, preparation, and sterilization, and container filling and closure are all separate processes.
Because of the level of automation of the entire process, little human intervention is required during manufacture compared to traditional aseptic filling and it is consid- ered an advanced aseptic filling process.
It is therefore possible to achieve very high levels of sterility confidence with a properly configured BFS machine designed to fill aseptically.
Encyclopedia of Pharmaceutical Science and Technology, Six Volume Set (Print)
Polymer granules are continuously fed to a machine hopper through an adiabatic screw extruder. It is then extruded through a die-and-pin set forming an open-ended tube of molten polymer known as a parison. It is therefore possible to achieve very high levels of sterility confidence with a properly configured BFS machine designed to fill aseptically. Polymer granules are continuously fed to a machine hopper through an adiabatic screw extruder.
It is then extruded through a die-and-pin set forming an open-ended tube of molten polymer known as a parison. The parison is supported by sterile air parison support air which is fed into its center through a sterilizing-grade air filter with oil- free compressed air. The parison is held in position by a clamp, which on some machines also serves to seal the parison bottom. A mold set consisting of two halves then moves over to the parison and closes around it. Molding is facilitated by vacuum slots in the mold.
The molded plastic is severed from the continuously extruding parison by a hot knife, and is shuttled within the mold set to the filling position. The filling mandrels are comprised of a set of filling tips which are held within a protective air shower; this is a small area within the filling machine which is typi- cally fed with sterile filtered air. When the molds are beneath the air shower, the filling tips are lowered into the neck of the partially formed container and the containers are filled.
The mandrels return to the protective air shower, and the containers are sealed 1 2 Blow-Fill-Seal Aseptic Processing by a second mold set head mold which forms the neck and closure of the BFS containers. The mold then opens and the filled containers surrounded by excess polymer are released. Ex- cess plastic is removed typically on line by means of a mold-specific cropping tool.
Liquid product is fed to the BFS machine from a holding tank or vessel.
Encyclopedia of Pharmaceutical Technology, Volume 20
The pathway is sterilized in place prior to receiving product, and product is sterilized by means of in-line sterilizing-grade filters. All good proton donors and acceptors are used in hydrogen bonding, six-membered ring intermolecular hydrogen bonds form in preference to intermolecular hydrogen bonds, the best proton donor and acceptor remaining after intermolecular hydrogen-bond formation will form intermolecular hydrogen bonds to one another but not all acceptors will necessarily interact with donors.
These observations help to address the issue of competing hydrogen bond assemblies observed when using a particular cocrystallising agent. A detailed understanding of the supramolecular chemistry of the functional groups present in a given molecule is the prerequisite for designing the co-crystals because it facilitates the selection of the suitable co-crystal former. Supramoecular synthons that can occur in common functional group in order to design new co-crystals and certain functional groups such as carboxylic acids, amides and alcohols are particularly amenable to formation of supramolecular heterosynthon[ 34 ].
This is partly because such a heteromeric system will only form if the non-covalent forces between two or more molecules are stronger than between the molecules in the corresponding homomeric crystals.
Design strategies for co-crystal formation are still being researched and the mechanism of formation is far from being understood[ 36 ]. Co-crystals can be prepared by solvent and solid based methods. The solvent-based methods involve slurry conversion solvent evaporation, cooling crystallization and precipitation. Solution co-crystallization: For solution co-crystallization, the two components must have similar solubility; otherwise the least soluble component will precipitate out exclusively.
However similar solubility alone will not guarantee success. It has been suggested that it may be useful to consider polymorphic compounds, which exist in more than one crystalline form as co-crystallising components.
If a molecular compound exists in several polymorphic forms it has demonstrated a structural flexibility and is not locked into a single type of crystalline lattice or packing mode. Thus, the chance of bringing such a molecule into a different packing arrangement in coexistence with another molecule is increased. Clearly polymorphism alone does not guarantee the functionality of a compound to act as a co-crystallising agent, whilst the ability of a molecule to participate in intermolecular interactions obviously plays a critical role[ 38 ].
Small-scale preparation has been described. Scale-up crystallization was performed in a ml water-jacketed glass crystallization vessel.
Temperature was maintained by a circulating water bath. A reflux column, digital thermometer, and overhead stirrer with a glass shaft and Teflon blade were attached to vessel ports. The drug and co-crystal former were added to a reaction vessel. Observe the appearance of the co-crystal. Literate to enhance solids recovery decrease the further temperature[ 21 ].
Grinding: When preparing co-crystals, the product obtained from grinding is generally consistent with that obtained from solution. This may indicate that hydrogen-bond connectivity patterns are not idiosyncratic or determined by non-specific and unmanageable solvent effects or crystallization conditions.
Nevertheless there are exceptions. Whilst many co-crystal materials can be prepared from both solution growth and solid-state grinding, some can only be obtained by solid-state grinding. An example is that in the co-crystallisation of 2,4,6-trinitrobenzoic acid and indoleacetic acid, different crystal forms were obtained from solution compared with grinding.
Failure to form co-crystals by grinding may be due to an inability to generate suitable co-crystal arrangements rather than due to the stability of the initial phases. When co-crystal formation has been successful from solution, but not from grinding, solvent inclusion in stabilizing the supramolecular structure may be a factor. Although co-crystal formation by solid-state grinding has been established for some time and a late 19th century report is often cited as the earliest reference to such a procedure, the recent technique of adding small mounts of solvent during the grinding process has been shown to enhance the kinetics and facilitate co-crystal formation and as lead to increased interest of solid-state grinding as a method for co-crystal preparation[ 38 ].
Slurry conversion: Slurry conversion experiments were conducted in different organic solvents and water. Solvent or ml was added to the co-crystal 20 mg and the resulting suspension was stirred at room temperature for some days. After some days, the solvent was decanted and the solid material was dried under a flow of nitrogen for 5 min. The remaining solids were then characterized using PXRD. Antisolvent addition: This is one of the methods for precipitation or recrystalization of the co-crystal former and active pharmaceutical ingredient.
Solvents include buffers pH and organic solvents. For example preparation of co-crystals of aceclofenac using chitosan, in which chitosan solution was prepared by soaking chitosan in glacial acetic acid. A weighed amount of the drug was dispersed in chitosan solution by using high dispersion homogenizer. This dispersion was added to distilled water or sodium citrate solution to precipitate chitosan on drug[ 39 ]. Habit describes the external shape of a crystal, where as polymorph state refers to the definite arrangement if molecules inside the crystal lattice[ 40 ].
Supersaturation, nucleation and crystal growth are the basic three steps in crystallization. Thermodynamic parameter like solubility, kinetical parameter like supersaturation, nucleation rate, dissolution rate, antisolvent addition rate, and evaporation rate phenomenon governs the crystallization[ 41 ].
From the above described methods such as solution crystallization, solvent change that create supersaturation by increasing the solute concentration and decreasing the solute solubility, respectively[ 41 ].
In case of increased saturation, rate of nuclei formation is greater than crystal growth. More growth in one direction produces fine needle shaped crystals that exhibit poor folowability, while less saturation leads to platy crystals which exhibit greater dissolution rate. Cooling a supersaturated solution of drug or pouring it into crystallizing solvent maintained at low temperature immediately decreases the drug solubility and results in rapid deposition of drug molecules on the nuclei.
Rapid cooling leads to formation of platy or needle shaped crystals, slow rate of cooling forms compact, symmetric or elongated prisms. The degree of solution agitation has influence on saturation level, high speed of agitation leads to elongated crystals with small particle size distribution having good folowability and less sedimentation in suspension.
Slow speed of agitation or unstirred solution forms large platy crystals. The nature of solvent has been found to have a profound effect on crystal habit of ibuprofen. Crystallization of ibuprofen from ethanol and acetone having high surface tension, dielectric constant and less specific gravity were thin, platy, and neatly circular in shape, while those obtained from propylene glycol and 2-propanol were rod shaped. When pH was decreased by addition of hydrochloric acid to sodium hydroxide solution pH resulted in formation of needle shaped crystals.
However, spherical agglomerates were obtained when ibuprofen was dissolved in acetonitrile because of limited miscibility with water[ 43 ]. Low temperature of crystallizing solvent produces irregular shaped crystals while in case of high temperature nuclei formation is delayed and fine, symmetric crystals are produced.
Ions, polymeric molecules, or the other substances present in solute or solvent acts as impurities for the growing crystals and modify crystal habit. Impurity is known to modify the growing crystals into a morphology that is desirable from the viewpoint of dosage form design and performance[ 44 ].
Grinding is well known to create lattice defects and amorphous phases, and the formation of polymorphic forms of drugs as a result of these stresses is well documented in the pharmaceutical literature.
Co-crystal formation during co-grinding and storage is mediated by amorphous phase, the rate of co-crystallization is dependent on the process and storage temperature, glass transition temperatures of reactants and additives, milling time and mill type[ 15 , 45 ]. They studied complex formation between macromolecules and certain pharmaceuticals.
However, these would not be classified as pharmaceutical co-crystals according to the criteria applied herein[ 46 , 47 ]. Perhaps the first application of crystal engineering to the generation of pharmaceutical co-crystals was a series of studies reported by Zerkowski et al. Despite their success in cocrystal formation, the focus of these studies was not so much the physical properties of the resulting co-crystals but rather the supramolecular functionality of barbitals and their complementarities with melamine.
Nevertheless, these studies illustrated very well the potential diversity of forms that can exist for a particular API as more than 60 co-crystals were structurally characterized in this series of studies. Clearly, such a diversity of forms could offer an exciting opportunity to novel and improved crystalline forms of APIs. Herein, we have chosen to focus upon several case studies that involve the formation of pharmaceutical co-crystals with altered physical properties of clinical relevance.
Oral administration of CBZ encounters multiple challenges, including low water solubility with high dosage required for therapeutic effect i. In contrast to its simple molecular structure, CBZ exhibits complexity in its crystal forms[ 20 , 21 ]. To date, four anhydrous polymorphs, a dihydrate, an acetone solvate, and two ammonium salts of CBZ have been identified. It is noted that, in the crystal structures of all these forms, the self-complementary nature of the amide group manifests itself in a predictable manner.
Therefore, CBZ has been used as an ideal candidate to demonstrate how APIs can be converted to pharmaceutical co-crystals, and how these co-crystals could offer optimized physicochemical properties over existing forms of an API[ 20 , 43 ]. Two strategies have been adopted for co-crystal formation of CBZ. One crystal engineering strategy is to employ the peripheral hydrogen bonding capabilities that are not engaged in the pure form of CBZ.
A second strategy for co-crystallization of CBZ involves breakage of the CBZ amide-amide dimer and formation of a supramolecular heterosynthon between CBZ and a co-crystal former[ 43 ]. Both strategies are successful and have afforded a number of CBZ co-crystals that exhibit improved physicochemical properties. For example, the CBZ:saccharin co-crystal shows significantly improved physical stability i.
In addition, the CBZ:saccharin cocrystal possesses favorable dissolution properties, suspension stability, and pharmacokinetics using dog models.
In short, the CBZ:saccharin cocrystal appears to be superior to existing crystal forms of CBZ in the following respects: stability relative to the anhydrous polymorph of CBZ; favorable dissolution and suspension stability, favorable oral absorption profile in dogs[ 49 ]. It is a solid under ambient conditions, only one crystalline phase is known, and it is available in the salt form.
It has been demonstrated that co-crystallization of this API modifies the physical properties of fluoxetine HCl while still retaining the hydrochloride salt of the API. Fluoxetine HCl was co-crystallized with benzoic acid , succinic acid , and fumaric acid via traditional evaporation techniques. For all three co-crystals, the carboxylic acid was found to form hydrogen bond to the chloride ion, which in turn interacted with the protonated amine, thus generating, in all three cases, amine hydrochloride salt hydrogen bonding to an additional neutral molecule.
Powder dissolution experiments were carried out in water for the three novel co-crystals resulting in a spread of dissolution profiles. However, the fluoxetine HCl: succinic acid cocrystal exhibited an approximately twofold increase in aqueous solubility after only 5 min. The complex formed between succinic acid and fluoxetine HCl falls apart in solution to generate its pure components after about 1 h.
An intriguing aspect of this study is that by simply hydrogen bonding a hydrochloride salt of an API with similar cocrystal formers, one can generate distinctively different dissolution profiles[ 50 ]. Itraconazole is extremely water insoluble and administered both orally and intravenously. Interestingly, no crystalline salt of itraconazole has been reported in the patent literature, even though salt formation using itraconazole and an acidic salt former would seem to be a logical approach to improve the absorption properties of the API.
In order to improve the absorption of the API and maintain the form crystallinity and stability, the pharmaceutical cocrystal approach has been evaluated in the formulation of itraconazole.
Crystalline phases of itraconazole can be engineered by introduction of additional molecules to match hydrogen-bond donors and acceptors[ 49 , 50 ]. A number of stable pharmaceutical co-crystals of itraconazole and 1,4-dicarboxylic acids were synthesized and crystallographically characterized[ 45 ].
Each cocrystal contains two API molecules and one acid cocrystal former, hydrogen- bonded through carboxylic acid—triazole supramolecular synthons, to form a trimeric assembly. The aqueous dissolution of itraconazole co-crystals was studied in order to assess their potential impact on bioavailability of the API.
The dissolution of itraconazole co-crystals was observed to behave more akin to the Sporanox form than to the crystalline form of the pure API. In particular, it was noted that the itraconazole:L-malic acid cocrystal exhibits a similar dissolution profile to that of the marketed formulation[ 49 ].
In a further pharmacokinetic study of itraconazole co-crystals, it was revealed that cocrystal formulation of the API gives similar oral bioavailability to the Sporanox form in the animal trial using a dog model[ 50 ]. In short; this study demonstrates the use of pharmaceutical co-crystals for the improvement of solubility and bioavailability without compromising crystallinity and stability. Sildenafil selectively inhibits cyclic guanosine monophosphate cGMP -specific phosphodiesterase type 5 that is responsible for degradation of cGMP in the corpus cavernosum, leading to smooth muscle relaxation in the corpus cavernosum, and resulting in increased inflow of blood and an erection.
It has been observed that sildenafil in a pharmaceutical cocrystal form could provide an improved solubility of the API under acidic conditions. In addition, such an improvement of solubility of sildenafil could be particularly advantageous for its orally administrable formulation. Sildenafil has been successfully co-crystallized with acetylsalicylic acid molar ratio by slurry or under reflux conditions. The crystal structure of the cocrystal of sildenafil and acetylsalicylic acid has been determined by single crystal X-ray diffraction, and in addition, the composition of matter was confirmed by powder X-ray diffraction and infrared spectrometry.
An intrinsic dissolution study in simulated gastric body fluid pH 1. Co-crystal of melamine and cyanuric acid: In early , the FDA received complaints from owners of more than pets regarding the deaths of animals after taking food that was later recalled; it was reported that majority of those deadly incidents were caused by acute renal failure.A nuclear pharmacist is expert at preparing compounding radiopharmaceuticals with Tcm sodium pertechnetate and a reagent kit.
Autoxidation and Antioxidants David M. Schoneker Novel forms or solid state phases of active pharmaceutical ingredients may be prepared for which there are no known polymorphs, solvates or hydrates, or where such polymorphs, solvates or hydrates were disfavored[ 62 ]. Popovich, N. When pH was decreased by addition of hydrochloric acid to sodium hydroxide solution pH resulted in formation of needle shaped crystals.
The mandrels return to the protective air shower, and the containers are sealed.
Impurity is known to modify the growing crystals into a morphology that is desirable from the viewpoint of dosage form design and performance[ 44 ].