Sandra Klein

Sandra Klein
University of Greifswald · Institute of Pharmacy

Prof. Dr.

About

101
Publications
54,375
Reads
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2,621
Citations
Citations since 2016
53 Research Items
1768 Citations
2016201720182019202020212022050100150200250300350
2016201720182019202020212022050100150200250300350
2016201720182019202020212022050100150200250300350
2016201720182019202020212022050100150200250300350
Additional affiliations
February 2010 - present
University of Greifswald
Position
  • Professor of Pharmaceutical Technology
December 2005 - January 2010
Goethe-Universität Frankfurt am Main
Position
  • Research Associate
July 2005 - November 2005
Eastman Chemical Company
Position
  • PostDoc Position

Publications

Publications (101)
Article
Full-text available
The present study focused on a new formulation approach to improving the solubility of drugs with poor aqueous solubility. A hot melt extrusion (HME) process was applied to prepare drug-loaded solid self-nanoemulsifying drug delivery systems (S-SNEDDS) by co-extrusion of liquid SNEDDS (L-SNEDDS) and different polymeric carriers. Experiments were pe...
Article
Full-text available
Biorelevant in vitro release models are valuable analytical tools for oral drug development but often tailored to gastrointestinal conditions in ‘average’ healthy adults. However, predicting in vivo performance in individual patients whose gastrointestinal conditions do not match those of healthy adults would be of great value for optimizing oral d...
Article
Full-text available
Self-nanoemulsifying drug delivery systems (SNEDDS) represent an interesting platform for improving the oral bioavailability of poorly soluble lipophilic drugs. While Liquid-SNEDDS (L-SNEDDS) effectively solubilize the drug in vivo , they have several drawbacks, including poor storage stability. Solid-SNEDDS (S-SNEDDS) combine the advantages of L-S...
Article
Full-text available
Selecting the appropriate formulation and solubility-enabling technology for poorly water soluble drugs is an essential element in the development of formulations for paediatric patients. Different methodologies and structured strategies are available to select a suitable approach and guide formulation scientists for development of adult formulatio...
Article
Full-text available
The majority of new drug entities exhibits poor water solubility and therefore enabling formulations are often needed to ensure sufficient in vivo bioavailability upon oral administration. Several in vitro tools have been proposed for biopredictive screening of such drug formulations to facilitate formulation development. Among these, combined diss...
Chapter
After oral administration of modified‐release (MR) formulations, a broad range of release patterns can be obtained and thus, at least theoretically, oral MR formulations can be tailored to the needs of specific patient populations. This chapter discusses the dissolution equipment that is currently used for the in vitro evaluation of dosage forms. I...
Article
Full-text available
The present study covers the synthesis, purification and evaluation of a novel aminomethacrylate-based copolymer in terms of its suitability for improving the solubility and in vitro release of poorly water-soluble drug compounds. The new copolymer was synthesized by solvent polymerization with radical initiation and by use of a chain transfer agen...
Article
Full-text available
Purpose Mixing with liquids or soft foods is a common procedure to improve acceptability of oral medicines in children but may affect drug stability and the in vivo performance of the administered drug product. The aim of the present study was to obtain an overview of the variability of critical attributes of commonly used vehicles and to identify...
Article
Full-text available
The present study focused on establishing a novel, (pre-)screening approach that enables the development of promising performing self-nanoemulsifying drug delivery systems (SNEDDSs) with a limited number of experiments. The strategic approach was based on first identifying appropriate excipients (oils/lipids, surfactants, and co-solvents) providing...
Article
Despite much progress in regulations to improve paediatric drug development, there remains a significant need to develop better medications for children. For the design of oral dosage forms, a detailed understanding of the specific gastrointestinal (GI) conditions in children of different age categories and how they differ from GI conditions in adu...
Article
For many years subcutaneous (SC) administration has represented the main route for delivering biopharmaceuticals. However, little information exists about the milieu in the subcutaneous tissue, especially about the properties/composition of the fluid present in this tissue, the interstitial fluid (ISF), which is one of the key elements for the drug...
Article
Enteral nutrition plays an important role for patients who are unable to properly swallow food. In such patients, enteral feeding tubes are often used, through which food, but often also oral medications, are administered. However, this can pose risk of tube clogging. Compared to the administration of crushed tablets, multiparticulate dosage forms...
Article
Improved global access to novel age‐appropriate formulations for paediatric subsets, either of new chemical entities or existing drugs, is a priority to ensure that medicines meet the needs of these patients. However, despite regulatory incentives, the introduction to the market of paediatric formulations still lags behind adult products. This is m...
Article
Since co-administration of dosage forms with food can impact drug exposure, food effect studies became an integral part of oral drug product development. Studies are usually performed in healthy adults and the dosage form is co-administered with a high-fat high-calorie standard breakfast meal to mimic worst-case dosing conditions. A corresponding s...
Article
A workshop on “Pediatric Formulation Development: Challenges of Today and Strategies for Tomorrow” was organized jointly by the University of Maryland’s Center of Excellence in Regulatory Science and Innovation (M-CERSI), the U.S. Food and Drug Administration (FDA) and the International Consortium for Innovation and Quality in Pharmaceutical Develo...
Article
Full-text available
Purpose: The objective of the present work was to screen whether a novel pediatric hydrocortisone granule formulation can be co-administered with common food matrices and liquids. Methods: Pediatric hydrocortisone granules were studied using a biopredictive in vitro approach. Experiments included an in situ chemical compatibility study of active...
Article
More than 10 years after the Paediatric Regulation came into place there is still a strong need for pure paediatric medicines for off-patent drug substances. Numerous compounds for which a paediatric formulation does not exist can be found on the WHO Model List of Essential Medicines for Children and in the EMA Inventory of the Needs for Paediatric...
Article
During the OrBiTo project, our knowledge of the gastrointestinal environment has improved substantially and biorelevant media composition have been refined. The aim of this study was to propose optimized biorelevant testing conditions for modified release products, to evaluate the reproducibility of the optimized compendial apparatus III (USP appar...
Article
This paper presents the output of a workshop held at the 11 th Annual Conference of EuPFI (European Paediatric Formulation Initiative), in September 2019 in Malmo, Sweden, on the development of multiparticulates and minitablets as pediatric formulations. The workshop focused on three specific facets of pediatric drug development, namely selection o...
Article
Full-text available
The release and absorption profile of an oral medication is influenced by the physicochemical properties of the drug and its formulation, as well as by the anatomy and physiology of the gastrointestinal (GI) tract. During drug development the bioavailability of a new drug is typically assessed in early clinical studies in a healthy adult population...
Chapter
Intravaginal drug delivery is particularly appropriate for drugs associated with women's health issues but may also have applications in general drug delivery within the female population. Intrauterine devices (IUDs) have historically been used as a method of contraception. Whereas for a long time intrauterine delivery had focused upon the use of c...
Article
Full-text available
The vagina is a promising site for both local and systemic drug delivery and represents an interesting administration route for compounds with poor oral bioavailability. Whereas most of the currently marketed dosage forms were designed as immediate release formulations, intravaginal rings (IVRs) offer the possibility of a controlled vaginal drug de...
Chapter
Rectal dosage forms (RDFs) have been applied for both systemic and local action for quite a long time. Rectal administration of drugs can be utilized for both local and systemic drug delivery. For drugs with systemic action the rectal route represents a useful alternative for patients that are unwilling or unable to be medicated orally. In vitro dr...
Article
Accurate prediction of oral absorption of drugs relies on biorelevant methodology. Current methods are based on Western healthy adult populations. Malnourished children have many differences in their gastrointestinal anatomy and physiology compared to a healthy Western adult. These differences may affect the oral absorption of medicines and it is i...
Article
The efficacy of narrow therapeutic index (NTI) drugs is closely related to their plasma concentration-time profile. Particularly for these compounds interindividual variability of gastrointestinal (GI) parameters relevant to in vivo drug release may result in fluctuations of the plasma concentration. The present study focused on assessing the influ...
Article
Lozenges are commonly applied in the treatment of sore throat. They often contain drugs intended to exert their effect locally in the oral cavity and throat. In the recent past, an increasing interest in development of generic products for locally acting lozenges could be noted. However, it was not clear, if therapeutic equivalence of locally appli...
Article
Alkindi® is a novel oral multi-particulate taste-masked formulation of hydrocortisone for use in children with the rare disease adrenal insufficiency. The objective of the present work was to study the biorelevant dissolution and compatibility properties of Alkindi® granules following exposure to administration fluids including breast milk, artific...
Article
Full-text available
There has been a trend towards the development of novel vaginal dosage forms both for local therapy and systemic absorption. The growing number of vaginal dosage forms, however, presents with an increasing demand for appropriate in vitro test methods for ensuring a safe and reliable in vivo performance of each of the formulations. Application of bi...
Article
Robust in vitro drug release behavior is an important feature of extended release (ER) hydrophilic matrix formulations for accurate prediction of in vivo drug release. In this study, ER hydrophilic matrix tablets of metoprolol tartrate were formulated using a high viscosity grade of hypromellose as a rate-limiting polymer. Expectedly, this formulat...
Article
Full-text available
Drug release and availability at the site of action are the major factors determining the clinical response for locally-acting gastrointestinal (GI) drug products. The present work focused on the prediction of site and extent of in vivo mesalazine release after oral administration to a variety of subjects using individualized in vitro drug release...
Article
Full-text available
Drug formulations based on lipids can enable a significantly better delivery of a pharmaceutically active substance and thus enhance their bioavailability. However, natural fats and oils usually have properties, which do not allow their direct use for drug delivery. Therefore, we have modified palm kernel oil (PKO) and shea butter (SB) via lipase-c...
Article
Locally-acting lozenges are among the most common types of solid dosage forms applied in the oral cavity. Since no guidance on the in vitro demonstration of local bioequivalence is available, we wanted to develop a new bio-predictive test method for dissolution of lozenges based on a set of physiological parameters relevant to lozenge dissolution i...
Article
Parkinson's disease (PD) is a progressive neurodegenerative disease that presents with visible motor symptoms, but that is accompanied by several additional symptoms, including gastrointestinal symptoms that may affect pharmacokinetics of oral medications. A detailed understanding of the nature of PD-specific gastrointestinal parameters and of how...
Article
The number of intramuscularly applied dosage forms has been continuously increasing during the last decades. However, up to date no in vitro dissolution test method for parenteral dosage forms has been described in the Ph. Eur. or USP. It was the aim of this study to investigate dissolution test setups based on the compendial flow-through cell and...
Article
The acceptability of pediatric pharmaceutical products to patients and their caregivers can have a profound impact on the resulting therapeutic outcome. However, existing methodology and approaches used for acceptability assessments for pediatric products is fragmented, making robust and consistent product evaluations difficult. A pediatric formula...
Article
Full-text available
Purpose: A variety of fixed-dose combination products is used in the therapy of Parkinson Disease. However, to date a proper analytical method applicable for comparative screening of different antiparkinson products was not available. The objective of the present work was thus to develop and validate an analytical method for the simultaneous quant...
Article
Objectives: The objective of this test series was to elucidate the importance of selecting the right media composition for a biopredictive in-vitro dissolution screening of enteric-coated dosage forms. Methods: Drug release from immediate-release (IR) and enteric-coated (EC) aspirin formulations was assessed in phosphate-based and bicarbonate-ba...
Chapter
The objective of developing oral MR multiparticulates is to release drugs in a controlled and predetermined fashion and/or to target to selective sites in the gastrointestinal (GI) tract. Dissolution test methods are an important tool both in quality control and prediction of the in vivo performance of oral multiparticulates. Before applying or des...
Article
A small amount of food is commonly used to aid administration of medicines to children to improve palatability and/or swallowability. However the impact of this co-administered food on the absorption and subsequent pharmacokinetic profile of the drug is unknown. Existing information on food effects is limited to standard protocols used to evaluate...
Article
Predictive in vitro test methods addressing the parameters relevant to drug release in the pediatric gastrointestinal tract could be an appropriate means for reducing the number of in vivo studies in children. However, dissolution models addressing the particular features of pediatric gastrointestinal physiology and typical pediatric dosing scenari...
Article
Accelerated drug release testing is a valuable quality control tool for long-acting non-oral extended release formulations. Currently, several intravaginal ring candidates designed for the long-term delivery of steroids or anti-infective drugs are being in the developing pipeline. The present article addresses the demand for accelerated drug releas...
Article
The aim of this research survey was to understand current global thinking around the need for and development of a paediatric biopharmaceutics classification system (pBCS) to be used for the development of paediatric medicines and regulatory purposes (e.g. Biowaivers). A literature review highlighted the paucity of data in this area and therefore a...
Article
Full-text available
Oral drug administration to children poses specific pharmaceutical challenges that are often not seen to the same extent in adults, and whose occurrence may also be age dependent. When an age-appropriate dosage form is not available, manipulation of adult dosage forms (e.g., splitting and crushing of tablets or opening of capsules) has been reporte...
Article
Full-text available
There is - apart from clinical trials - an ongoing discussion on how to demonstrate therapeutic equivalence for locally applied and locally acting products in the gastrointestinal tract. Possibly, among other alternatives, in vitro drug release models could be considered surrogates of drug release and availability at the site of action. However, to...
Article
Full-text available
Dissolution testing is an in vitro procedure which is widely used in quality control (QC) of solid oral dosage forms and, given that real biorelevant test conditions are applied, can also be used as a predictive tool for the in vivo performance of such formulations. However, if a dissolution method is intended to be used for such purposes, it has t...
Article
The complex process of oral drug absorption is influenced by a host of drug and formulation properties as well as their interaction with the gastrointestinal environment in terms of drug solubility, dissolution, permeability and pre-systemic metabolism. For adult dosage forms the use of biopharmaceutical tools to aid in the design and development o...
Article
The hydrogen carbonate buffer is considered as the most biorelevant buffer system for the simulation of intestinal conditions and covers the physiological pH range of the luminal fluids from pH 5.5 to about pH 8.4. The pH value of a hydrogen carbonate buffer is the result of a complex and dynamic interplay of the concentration of hydrogen carbonate...
Article
The aim of the present series of experiments was to compare various in vitro tools including evaluation of formulations influence on solubility, various dissolution tests, and an updated, miniaturized transfer model to forecast the behavior of novel formulations of the poorly soluble, weakly basic model compound ketoconazole (KETO) after oral admin...
Article
Accurate prediction of the in vivo biopharmaceutical performance of oral drug formulations is critical to efficient drug development. Traditionally, in vitro evaluation of oral drug formulations has focused on disintegration and dissolution testing for quality control (QC) purposes. The connection with in vivo biopharmaceutical performance has ofte...
Article
Proton pump inhibitors are potent gastric acid-suppressing agents and belong to the most widely sold drugs in the world. However, even though these antisecretory agents are regarded as safe, they can show several interactions with co-administered drugs. Due to the suppression of gastric acid secretion, the can significantly alter the intragastric p...
Article
Full-text available
In the past decades, the vertical diffusion cell has emerged as a useful device for testing drug release of topical dosage forms. However, to date neither a general USP method nor formulation-related monographs have been published in international pharmacopoeia. The purpose of the present work was to examine the influence of different test paramete...
Article
The objective of the present study was to investigate if temperature can be utilized to accelerate drug release from Nuvaring(®), a reservoir type intravaginal ring based on polyethylene vinyl acetate copolymer that releases a constant dose of contraceptive steroids over a duration of three weeks. The reciprocating holder apparatus (USP 7) was util...
Article
Purpose: Design of biorelevant test setups mimicking the physiological conditions experienced by drugs after oral administration along the passage through the mouth and the GI tract for the in vitro evaluation of diclofenac exhibiting multiple-peak phenomenon during absorption. Methods: The biorelevant models simulated successively saliva (SSF,...
Article
Full-text available
The bicarbonate buffer is considered as the most biorelevant buffer system for the simulation of intestinal conditions. However, its use in dissolution testing of solid oral dosage forms is very limited. The reason for this is the thermodynamic instability of the solution containing hydrogen carbonate ions and carbonic acid. The spontaneous loss of...
Article
The objective of the present study was to check for the possibility to successfully predict individual in vivo dissolution / absorption profiles resulting from fasted administration of a diclofenac extended release pellet formulation. For this purpose dissolution profiles were generated with different dissolution setups using a set of media reflect...
Article
Low aqueous solubility is often a limiting aspect to the bioavailability of poorly soluble, but highly permeable drugs (class II compounds according to the Biopharmaceutics Classification System – BCS) administered in single drug products or as fixed dose combinations. The aim of the present series of experiments was to improve the solubility and d...
Article
The aim of the present series of experiments was to improve the solubility and dissolution/precipitation behaviour of a poorly soluble, weakly basic drug, using itraconazole as a case example. Binary inclusion complexes of itraconazole with two commonly used cyclodextrin derivatives and a recently introduced cyclodextrin derivative were prepared. T...
Article
For poorly soluble weak bases, the possibility of drug precipitation upon entry into the small intestine may affect the amount of drug available for uptake through the intestinal mucosa. A few years ago, a transfer model was introduced which has been developed to simulate the transfer of a dissolved drug out of the stomach into the small intestine....
Article
The in-vivo performance of oral modified-release dosage forms is determined by the interplay of various physiological- and dosage-form-derived parameters. Thus it is often a challenge to predict the in-vivo drug-release behaviour from modified-release dosage forms based solely on in-vitro release rates. For a long time the most common procedure to...