SPECTROSCOPIC OBSERVATIONS ON RELAXATION IN LIQUID HALO AROMATICS

Present address of Douglas Swanson: IBM Corporation, Rochester, Minnesota, 55901. Heine K\""{o}ser has been on leave from Instit\""{u}t f\""{u}r Chemische Technologie der Technischen, Universit\""{a}t Clausthal, 3392 Clausthal-Zellerfeld, West Germany.""Author Institution: Department of Chemistry, University of Minnesota; University of Tennessee, University of MinnesotaIn connection with our program of investigation on relaxation processes in liquids, including vibrational and rotational relaxation in particular, we have been evaluating measurements of Infrared band shapes for the calculation of the correlation function and have begun to employ Raman observations along with the infrared band shapes to obtain information on the relaxation processes. In particular, we have sought to obtain the most accurate band shapes possible, so that the resulting Fourier transforms may be as reliable as possible in their details. We have applied these methods, both Raman and infrared, to chlorobenzene, fluorobenzene, iodobenzene, pyridine, and their perdeutero isotopes. These constitute an interesting set of related molecules whose rotational and vibrational dynamics may be expected to be reasonably ""normal."" In connection with the experimental technique and the reduction of data, some discussion will be presented regarding the difficulties of significant or variable ""base lines"", and methods of minimizing these problems

Development of a process using electron beam for a terminal sterilization for parenteral formulations of pharmaceuticals

As pharmaceutical technology advances and sensitive drug formulations demand ever-greater stability, radiation processing is likely the only alternative that can be used to terminally sterilize thermo-labile pharmaceutical products intended for parenteral administration. To this end, a radiation process using e-beam technology has been developed. A key feature of this process is the elucidation of defined conditions of radiation processing in order to achieve the homogeneity of the absorbed dose inside a single vial and throughout a tray containing several vials. Results of several dosimetry studies, using e-beam technology, demonstrate the beneficial effects of the use of aluminum or stainless-steel plates to scatter the beam and therefore to Obtain an excellent D-max/D-min across all dose-monitoring positions within the vial and throughout a tray containing 260 vials filled with a dry powder or a tray containing approximately 30 vials filled with an aqueous solution. This ionizing radiation process can be directly applicable, at a manufacturing level, for a terminal sterilization of parenteral formulations of pharmaceuticals. (C) 2004 Elsevier Ltd. All rights reserved

Meeting report: FIP/AAPS joint workshop report: Dissolution/in vitro release testing of novel/special dosage forms

In 2003, the FIP Dissolution Working group published a position paper on dissolution/drug release testing for special/ novel dosage forms that represented the scientific opinions of many experts in the field at that time (1). The position paper has supported activities, programs, and decisions in the scientific, technical, and regulatory community. Due to the rapid evolution of new practices and techniques for in vitro testing, the FIP Special Interest Group (SIG) on Dissolution/ Drug Release decided to revise the previous paper and added proposals for further harmonization of in vitro release testing practices for different pharmaceutical dosage forms. This article represents the current updates to the previously published paper. This revision has been aligned to coincide with the USP taxonomy including route of administration, intended site of drug release, and dosage form. The revised paper includes information from current literature, expert discussions, and presentations from recent workshops (2, 3). The authors acknowledge and expect further updates to be made as additional progress is made in the relevant areas. Thus, comments and additional contributions are welcome and may be considered for the next revision of the position paper. The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration or other licensing authorities and should not be construed to represent any agency determination or policy

Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, II: investigations of mechanism

<p>Abstract</p> <p>Background</p> <p>Olanzapine long-acting injection (LAI) is a salt-based depot antipsychotic combining olanzapine and pamoic acid. The slow intramuscular dissolution of this practically insoluble salt produces an extended release of olanzapine lasting up to 4 weeks. However, in a small number of injections (< 0.1%), patients experienced symptoms suggestive of olanzapine overdose, a phenomenon that has been termed "post-injection delirium/sedation syndrome" (PDSS). The authors conducted a series of parallel investigations into the possible reasons PDSS events occur.</p> <p>Methods</p> <p>Healthcare providers involved in the PDSS cases were queried for clinical information around the events. Plasma samples from patients experiencing PDSS were collected when possible (12/30 cases) and olanzapine concentrations compared with the known pharmacokinetic profile for olanzapine LAI. Product batches and used vials from the PDSS cases were evaluated for compliance with established manufacturing standards and/or possible user error. Because this depot formulation depends upon slow dissolution at the intramuscular injection site, in-vitro experiments were conducted to assess solubility of olanzapine pamoate in various media.</p> <p>Results</p> <p>Injection administrators reported no unusual occurrences during the injection. No anomalies were found with the product batches or the remaining suspension in the used vials. Olanzapine concentrations during PDSS events were higher than the expected 5-73 ng/mL range, with concentrations exceeding 100 ng/mL and in some cases reaching >600 ng/mL during the first hours after injection but then returning to the expected therapeutic range within 24 to 72 hours. Solubility and dissolution rate of olanzapine pamoate were also found to be substantially greater in plasma than in other media such as those approximating the environment in muscle tissue.</p> <p>Conclusions</p> <p>Manufacturing irregularities, improper drug reconstitution, and inappropriate dosing were ruled out as possible causes of PDSS. In-vitro solubility and in-vivo pharmacokinetic investigations suggest that PDSS is related to exposure of the injected product to a substantial volume of blood. This exposure is most likely the result of unintended partial intravascular injection or blood vessel injury during the injection (occurring even with proper injection technique) with subsequent seepage of the medication into the vasculature, which would produce higher than intended olanzapine concentrations and symptoms consistent with PDSS.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID; URL: <url>http://http//www.clinicaltrials.gov/</url>: NCT00094640, NCT00088478, NCT00088491, NCT00088465, and NCT00320489</p

FIP Position Paper on Qualification of Paddle and Basket Dissolution Apparatus

The qualification process for ensuring that a paddle or basket apparatus is suitable for its intended use is a highly debated and controversial topic. Different instrument qualification and suitability methods have been proposed by the pharmacopeias and regulatory bodies. In an effort to internationally harmonize dissolution apparatus suitability requirements, the International Pharmaceutical Federation's (FIP) Dissolution/Drug Release Special Interest Group (SIG) reviewed current instrument suitability requirements listed in the US, European, and Japanese pharmacopeias and the International Conference on Harmonization (ICH) Topic Q4B on harmonization of pharmacopoeial methods, in its Annex 7, Dissolution Test General. In addition, the SIG reviewed the Food and Drug Administration (FDA) Draft Guidance for Industry, “The Use of Mechanical Calibration of Dissolution Apparatus 1 and 2—Current Good Manufacturing Practice (CGMP)” and the related ASTM Standard E2503-07. Based on this review and several in-depth discussions, the FIP Dissolution/Drug Release SIG recommends that the qualification of a dissolution test instrument should be performed following the calibration requirements as indicated in the FDA (draft) guidance. If additional system performance information is desired, a performance verification test using US Pharmacopeia Reference Standard tablet or an established in-house reference product can be conducted. Any strict requirement on the use of a specific performance verification test tablet is not recommended at this time

FIP/AAPS Joint Workshop Report: Dissolution/In Vitro Release Testing of Novel/Special Dosage Forms

In 2003, the FIP Dissolution Working group published a position paper on dissolution/drug release testing for special/novel dosage forms that represented the scientific opinions of many experts in the field at that time (1). The position paper has supported activities, programs, and decisions in the scientific, technical, and regulatory community. Due to the rapid evolution of new practices and techniques for in vitro testing, the FIP Special Interest Group (SIG) on Dissolution/Drug Release decided to revise the previous paper and added proposals for further harmonization of in vitro release testing practices for different pharmaceutical dosage forms. This article represents the current updates to the previously published paper. This revision has been aligned to coincide with the USP taxonomy including route of administration, intended site of drug release, and dosage form. The revised paper includes information from current literature, expert discussions, and presentations from recent workshops (2,3). The authors acknowledge and expect further updates to be made as additional progress is made in the relevant areas. Thus, comments and additional contributions are welcome and may be considered for the next revision of the position paper