Showing papers in "Pharmaceutical technology in 2000"

Fast-dissolving tablets

Abstract: Fast-dissolving tablet technologies are important for patients who have difficulty taking conventional oral dosage forms as well as for pharmeceutical firms seeking line extensions in the marketplace. This artide describes existing fast-dissolving technologies and discusses several techniques used to formulate such tablets, namely tablet molding, freeze-drying, spray-drying, sublimation, disintegrant addition, and the use of sugar-based excipients.

On powder flowability

Abstract: The term powder flowability is used loosely and has generally been more closely associated to the test method used to measure it than the significance to the process. To the formulator, flowability is linked to the product. To the engineer, flowability relates to the process. Relating powder flowability results to actual behavior in the production process is the true reason flowability is measured. This article connects typical powder handling processes to flow property measurements of value to the formulator and the process engineer.

Prolonged Gastric Retention Using Floating Dosage Forms

Abstract: Prolonging the gastric retention of dosage forms can provide therapeutic benefits such as local treatment and enhanced bioavailability.This article describes some of the ways to achieve gastric retention, including the authors' work on dosage forms designed to float on the contents of the stomach and prevent premature emptying.

Roll compaction granulation of a controlled-release matrix tablet formulation containing HPMC: Effect of process scale-up on robustness of tablets, tablet stability and predicted in vivo performance

Abstract: A theophylline controlled release formulation was dry granulated using a laboratory-scale roller compactor. Roll pressure, screw speed, and roll speed were optimized and used to determine the direct scale-up equipment parameters. The tablet formulation then was scaled up to pilot scale and full production-scale roller compaction equipment. Direct scale-up involved the use of linear roll speed and compaction force per linear inch of roll width, Dry granulations were evaluated at several equipment variable settings established during the direct scale-up stage. Granulations and tablets prepared from the granulations were tested for physical properties and drug dissolution. Similarity in drug-release characteristics was determined by using f 2 metric analysis. Accelerated and ambient stability tests were performed on prepared tablets. Stability testing showed no major changes in tablet physical properties and drug release.

Perspective from a large CRO: Project management of Small R&D Companies, part II

Abstract: Eighty-five percent of solid drugs in Europe are packed in blisters, compared with less than 20% of those in the United States. However, blister packaging is becoming more accepted in the United States as both manufacturers and consumers recognize its benefits. This article discusses the materials used for blister packages and typical blister constructions.

The physics of powder flow : Applied to pharmaceutical solids

Abstract: Pharmaceutical scientists working in powder processing can benefit from the physics literature on studies of granular materials. This article summarizes some important findings relevant to vibration, mixing, milling, and characterization of pharmaceutical powders.

Aqueous enteric coatings with methacrylic acid copolymer type C on acidic and basic drugs in tablets and pellets, part II : Dosage forms containing indomethacin and diclofenac sodium

Abstract: The authors applied an aqueous enteric film formulation containing methacrylic acid copolymer type C, a pigment mixture, and a plasticizer to acidic indomethacin (IND) pellets and alkaline diclofenac sodium (DIC) pellets and tablets. Both types of pellets absorbed much more fluid during the gastric resistance test than did identically coated acetylsalicylic acid (ASA) crystals. DIC pellets absorbed more fluid than did IND pellets. Because no drug release was detected in simulated gastric fluid, DIC and IND pellets with film thicknesses of 3 mg/cm 2 satisfied USP requirements for resistance to gastric fluid. To meet USP requirements, the lower resistance of film-coated DIC tablets to gastric fluid compared with film-coated ASA tablets must be compensated for by increasing the film thickness to 4 mg/cm 2 .

Comparison of in vitro dissolution profiles: Using a novel, model-independent approach

Abstract: This article describes a novel, model-independent mathematical method for evaluating the difference between the percentage or amount of drug dissolved from a reference formulation and that dissolved from a test formulation. A new similarity factor (S d ) expresses the percentage difference between two dissolution profiles. Major advantages of the method are simplicity and ease of interpretation.The authors compared in vitro dissolution data from sustained-release tablets of diltiazem HCl with that of a reference product using the dissimilarity factor (f 1 ), similarity factor (f 2 ), Rescigno indices (ξ 1 and ξ 2 ),S d , the ratio of the mean percentage of dissolved drug, and the mean dissolution time. The percentage difference between the test and reference formulations was small.The difference between the results of two immediate-release commercial formulations was large.

Aqueous enteric coatings with methacrylic acid copolymer type C on acidic and basic drugs in tablets and pellets, Part I : Acetylsalicylic acid tablets and crystals

Abstract: The authors applied an aqueous enteric film formulation developed on caffeine cores containing methyacrylic acid copolymer type C (as a film former), a pigment mixture, a plasticizer, and talc to tablets and crystals of the hydrolysis-sensitive, acidic drug acetylsalicylic acid. With both dosage forms a film thickness of 3 mg/cm 2 was sufficient to achieve good resistance to gastric fluid, i.e., low values for gastric fluid absorption, drug release, and hydrolysis of the drug during a 2-h test in 0.1 N HCI.

Pharmaceutical blister packaging, part II: Machinery and assembly

Abstract: Blister packaging and labeling is quickly being recognized as a beneficial tool in helping manufacturers protect and promote their products and meet new regulations. Part II of this article reviews the machinery, assembly, and costs of blister packaging and discusses how clinical trials and recent regulatory developments will grow the blister packaging industry in the United State.

Establishing scientifically justified acceptance criteria for the cleaning validation of APIs

Abstract: Setting limits based on sound scientific principles is critical for cleaning validation protocols. Residues in the manufacture of active pharmaceutical ingredients (APIs) must be considered directly because of possible effects on any subsequently manufactured API and, ultimately, regarding how such APIs are used in finished drug products. The author presents equations for calculating various aspects of residue limits for APIs.

Sustained-release tablets via direct compression: A feasibility study using cellulose acetate and cellulose acetate butyrate

Abstract: The authors demonstrate the feasibility of using cellulose acetate (CA) and cellulose acetate butyrate (CAB) for formulating sustained-release tablets via direct compression. Results show that tablets exhibited a slower release rate when CAB was used in the tablet matrix than when CA was used as the matrix material, which suggests that the release mechanisms from CA and CAB may be different.

Photostability studies of drug substances and products practical implications of the ich guideline

Abstract: The authors studied the photostability characteristics of a drug substance and its formulated product according to the conditions proposed in ICH's guideline on photostability. Two photostability apparatuses were designed on the basis of Option 2 recommendations. The results indicate that the conditions provide insufficient details to ensure reproducibility. The current ICH recommendations are subject to different interpretations and therefore need further improvements and better standardization.

How to establish an effective maintenance program for cleaning validation

Abstract: For the past decade, cleaning validation has been a challenge for most pharmaceutical firms. It is a recurrent problem during EDA inspections, even though many companies have now implemented cleaning validation programs (1). There is a strong need to improve the design of such programs and to implement effective maintenance programs after the cleaning validation study has been completed. The author recommends a scientific and systematic approach for designing a cleaning validation study and its maintenance program to maximize and sustain the validity of a cleaning validation program.

Applying HACCP to pharmaceutical process validation

Abstract: Use of the hazard analysis and critical control points (HACCP) system for identifying and controlling critical process steps now is considered current by FDA's Center for Devices and Radiological Health. The approach could become accepted and expected as a result of the regulatory mandates for production and process controls.This article presents some ideas for applying the HACCP program to any process application.

Particle-size analysis of pharmaceutical aerosols

Abstract: The last decade of the 20th century was the most active for the particle-size analysis of pharmaceutical aerosols. Increased interest in methods development, representative sampling, and particle-size measurement led to a better understanding of the advantages and limitations of these methods as applied to inhalation products. Now that we have have entered a new millinnium, it may be useful to document current thinking and speculate on the future of the particle-size analysis of therapeutic aerosols.

The FDA regulatory methods validation program for new and abbreviated new drug applications

Abstract: This article describes the U.S. Food and Drug Administration (FDA) methods validation program for proposed regulatory methods submitted through the New and Abbreviated New Drug Application processes. The program is conducted by the Center for Drug Evaluation and Research (CDER) and the Office of Regulatory Affairs to ensure that scientifically well-founded regulatory methods are available to assess the quality of the CDER-approved products. The industry, FDA, and United States Pharmacopeia and National Formulary have the common objective of ensuring that drugs in the U.S. marketplace have consistent standards for drug substances and drug product regardless of the synthesis and manufacturing process. This may be accomplished by assuring that the analytical methods for new drug products are submitted for adoption as public standards soon after approval for marketing. The public standard provides a yard-stick for the named product which allows conscientious practitioners and consumers to determine if a product is as purported and thereby be able to detect spurious and sub-standard products in the marketplace. INTRODUCTION Validation of the analytical methods cited in a New Drug Application (NDA) or Abbreviated New Drug Application (ANDA) is an important part of the U.S. Food and Drug Administration (FDA) drug review process. This validation effort, which is usually performed in two FDA laboratories, together with the validation performed by an applicant provides up to three independent assessments of an applicant’s methods to reliably determine the identity, strength, quality, purity, and potency of an approved new drug product. This article provides an overview of the FDA methods validation program conducted by the Center for Drug Evaluation and Research (CDER) in collaboration with the Office of Regulatory Affairs (ORA) for approved new and generic drugs. This article was developed as part of an effort to improve the efficiency of this program. 1 With the repeal of Section 507 of the Food Drug & Cosmetic Act, the antibiotic designations, which distinguished them from other drug products, have been eliminated. Methods validation approaches and issues for antibiotic drug products continue as those for all other new drugs currently approved under 505(b) and 505(j). 2 The United States Pharmacopeial Convention, 12601 Twinbrook Parkway, Rockville, MD 20852.

Production of recombinant collagen for biomedical devices

Abstract: Collagens comprise a family of 19 proteins with a broad range of structural and physiological functions. Various biomaterials based on collagen I are available, and newly discovered collagens could be of major interest to the pharmaceutical industry. Considering the risks of using collagen from animal sources, recombinant production represents a valuable alternative.This article describes the most reliable systems for producing recombinant collagen, from the traditional E. coli expression system to emerging techniques using transgenic organisms.

Advances in nasal drug delivery devices and packaging

Abstract: Nasal delivery devices are not limited to local medical therapy. The nasal route is an alternative to invasive or oral drug administration. The penetration of bioactive molecules through the nasal mucosa has been shown to achieve good bioavailability, and nasal sprays offer patients greater convenience. This article reviews some of the latest devices for liquid and dry-powder formulations, including preservative-free systems, and the business benefits they offer.

X-ray diffraction II : Using single-crystal X-ray diffraction to study polymorphism and solvatomorphism

Abstract: The phenomenon of X-ray diffraction has found widespread use as a means to determine the structures of single crystals and represents the most powerful and direct method to obtain bond lengths and bond angles for molecules in the solid state. This information is of extreme importance to workers in pharmaceutics when they encounter the existence of polymorphism - the ability of a molecule to crystallize in more than one structure of the same degree of solvation - or solvatomorphism - the ability of a molecule to crystallize in different structures that in turn differ in their solvation state. This article examines how single-crystal X-ray diffraction has been used to study the types of molecular structures that can exist for polymorphic and solvatomorphic solids. ( This article was previously published in Spectroscopy 15 [7], 34-39 [2000]).

Artificial neural network and simplex optimization for mixing of aqueous-coated beads to obtain controlled-release formulations

Abstract: The authors explored the use of simplex optimization and artificial neural network (ANN) procedures to obtain coated beads with desired release characteristics by mixing several beads of known strengths and release characteristics. They compared the modeling and optimization abilities of simplex and ANN procedures and in this article present their results and conclusions.

Issues in evaluating the in-use photostability of transdermal patches

Abstract: Transdermal devices are unique with respect to in-use photostability, and current International Conference on Harmonization (ICH) guidelines do not address many of the issues involved. The authors used data collected for a transdermal device containing xanomeline to discuss some of these in-use photostability issues. This article describes why the thresholds for identification and quantification outlined in the ICH guidelines on impurities in new drug products should not be directly applied to transdermal devices.

Hydrofluoroethers as low-temperature heat-transfer fluids in the pharmaceutical industry

Abstract: This article describes two new hydrofluoroether heat-transfer fluids that are useful for low-temperature pharmaceutial processes. C 4 F 9 OCH 3 has been used in several commercial applications below 80°C(1). C 3 F 7 OCH 3 has been used with liquid nitrogen to cool a reaction vessel to 116°C (2). A theoretical analysis compares the heattransfer capabilities of these fluids to those of two conventional fluids. The new materials are nonflammable, low in toxicity, and have favorable environmental properties.

Development and validation of automated methods for finished product testing

Abstract: The use of automated sample preparation and dissolution methodologies is widespread in the pharmaceutical industry. However, guidance on the development and validation of these methods has been limited. The automation subgroup of the Pharmaceutical Analytical Sciences Group, which represents pharmaceutical companies with UK-based research and development operations, has pooled its expertise to produce a set of detailed guidelines. The hope is that this document, presented in this article, will allow both the novice and expert user to produce high-quality, robust, automated methodologies.

Trust : The secret of success for contract research organizations

Abstract: A successful relationship between a contract research organization and its client begins with trust. Establishing trust involves asking pertinent questions, recognizing the importance of good communication, and being aware of the warning signs.

Current issues in manufacturing and control

Abstract: Sterile manufacturing of prefilled syringes is experiencing significant growth worldwide. Processing and quality control of sterile prefilled syringes requires several unique and special considerations not applicable to vial, ampul, or other injectable packaging systems. This article will help the interested reader understand these requirements and provide valuable learning points for successful manufacturing of these unique dosage forms.

Considerations in using bubble point type tests as filter integrity tests, Part I : Effect of test methodology on filter cartridge bubble point measurements and implications for the use of bubble point type tests as correlated tests

Abstract: The term bubble point test refers to a colloection of many different test methods. In this Part I of a two-part article, the authors report on the effect of test methodology on bubble point measurements, including those using automated instruments. Results indicate that bubble points measured for the same filter cartridge can vary by ∼5-6 psi, depending on the exact bubble point type test used and that all tests dectected bubble points for the filter cartridges at pressures well above the intrinsic transition point marking the onset of bulk flow. The results clearly show that the use of bubble point specification as a correlated (critical) test on a process filter is most valid when the test is performed using the same specific protocol, equipment, and filter area used to establish the primary correlation in the first place.