Doctor of pharmacy as a career option: a cross-sectional study exploring PharmD students and practitioners expectations in Jordan.

OBJECTIVE: This study aimed to (1) investigate the expectations and preferences of PharmD students and practitioners regarding their role in the health care system, and (2) to contrast those expectations and preferences of PharmD practitioners with real-life practice in Jordan. METHODS: Two cross-sectional descriptive questionnaires were used to collect data from PharmD students and PharmD practitioners in Jordan. A total number of 330 students and 280 practitioners were interviewed. The responses to all questions were encoded, entered, and summarized as frequencies and percentages or as means and standard deviations. Comparisons between groups were performed using Chi-square test. A p-value of < 0.05 was considered significant. RESULTS: Both PharmD students and practitioners chose working as a clinical pharmacist in a hospital as their first-choice job. However, their second and third jobs choices were significantly different as practitioners opted for income as a main criterion for job selection. Interestingly, salary expectations by PharmD students were significantly higher than the reality as reported by PharmD practitioners. Both students and practitioners placed the work environment as the highest priority criterion for making a work choice on the work environment. In general, both students and practitioners agree on the ideal roles of PharmD graduate with the issues of prescribing and compounding responsibilities being the ones with the highest disparity between practitioners and students. Significant differences were found between the student's and practitioner's perceptions of the ideal role of a PharmD in and the current professional practice in Jordan. CONCLUSION: Job preferences and salary expectations differ significantly between students and practitioners. Professional orientation of PharmD. students should be implemented to minimize misconceptions of their job nature, availability, and compensations. The fact that students do not prefer to work in a community pharmacy should be addressed by educational institutions and professional organizations. The prescribing and compounding responsibilities of pharmacists should be also emphasized in the curricula of pharmacy schools and worked in by professional organization to achieve optimal implementation in real-life practice.

Preparation and evaluation of ascorbyl glucoside and ascorbic acid solid in oil nanodispersions for corneal epithelial wound healing.

The objective of this study was to develop and evaluate an effective topical formulation to promote corneal epithelial wound healing. Ascorbyl glucoside (AA-2G), a stable prodrug of AA, was formulated in solid in oil (S/O) nanodispersions by emulsifying AA-2G solutions in cyclohexane using Span 85 as an emulsifying agent and freeze-drying emulsions to produce AA-2G - surfactant complex. The complexes were then dispersed in castor oil to produce S/O nanodispersions which were evaluated in terms of their particle size, polydispersity index, encapsulation efficiency, morphology, physical stability as well as the transcorneal permeation and accumulation of AA-2G. The same preparation procedure was used to prepare S/O nanodispersions of AA. S/O nanodispersions of AA and AA-2G were formulated into oily drops that were tested for efficacy in promoting wound healing after corneal epithelial depredation. AA-2G was loaded efficiently in S/O nanodispersions (EE > 99%) in the form of spherical nanoparticles. S/O nanodispersions were physically stable and resulted in improved permeation (18x) and accumulation (7x) of AA-2G in transcorneal diffusion experiments in comparison to AA-2G solutions. Oily eye drops of AA-2G and AA showed no irritation and significant improvement in epithelial healing in vivo in comparison to AA-2G and AA solutions.

The cutaneous effects of long-term use of Dead Sea mud on healthy skin: a 4-week study.

PURPOSE: To investigate the effects of various types of Dead Sea mud (DSM) on skin barrier properties over a period of four weeks. METHODS: The effects of a 4-week application of three types of DSM (as is mud, mud with extra Dead Sea salt, and over the shelf mud) on the barrier properties of normal skin were investigated. Preparations were applied onto forearms of healthy volunteers every other day for 4 weeks, and skin hydration, transepidermal water loss (TEWL), melanin, erythema level, skin pH, skin elasticity, dermal thickness, and collagen content were measured at predefined circular areas on subjects' forearms at baseline, week 1, week 2, and week 4 during the treatment phase and on week 5 following a 1-week regression period in which no mud was applied. RESULTS: The use of DSM for 4 weeks was well tolerated with no noticeable changes in TEWL, skin pH, melanin, and erythema levels. A slight firming effect was observed in the forearms treated with salted DSM. Skin hydration was not significantly affected by any type of DSM. However, a slight drying effect of "as is" and "salted" DSM and slight hydration effect of "over the shelf" DSM were observed. This effect could be attributed to the content of DSM rather than to disruption of skin integrity as confirmed by TEWL values. CONCLUSION: Long-term use of all types of DSM did not compromise the barrier integrity of the skin. This provides dermatologists with needed information on safety of DSM and lack of skin disruption activity upon long-term use.

Hot melt extruded zein for controlled delivery of diclofenac sodium: Effect of drug loading and medium composition.

This study evaluates the potential use of zein as an excipient in hot-melt extrusion for controlled delivery of diclofenac sodium (DS). Mixtures of zein, polyethylene glycol and drug were hot melt extruded and cut into 2 mm extrudates. Extrudates were characterised using differential scanning calorimetry, X-ray powder diffraction and scanning electron microscopy. The drug in the extrudates was found to be in the non-crystalline state, independent of the drug loading. Moreover, the drug release from extrudates was investigated. The release was directly dependent on the drug loading: a controlled and nearly zero-order release was obtained at the lowest drug loading (12.5% w/w), whereas almost immediate release was achieved at higher drug loadings, i.e. 25% and 37.5%. The release was inversely dependent on the ionic strength of the medium. The influence of digestive enzymes on drug release was also studied. Pancreatin, but not pepsin, was found to have a significant influence on the drug release as well as on the microstructure of zein extrudates. These data therefore support the potential use of zein as excipient in hot melt extrusion for controlled release purposes.

Evaluation of the effect of items' format and type on psychometric properties of sixth year pharmacy students clinical clerkship assessment items.

BACKGROUND: Examinations are the traditional assessment tools. In addition to measurement of learning, exams are used to guide the improvement of academic programs. The current study attempted to evaluate the quality of assessment items of sixth year clinical clerkships examinations as a function of assessment items format and type/structure and to assess the effect of the number of response choices on the characteristics of MCQs as assessment items. METHODS: A total of 173 assessment items used in the examinations of sixth year clinical clerkships of a PharmD program were included. Items were classified as case based or noncase based and as MCQs or open-ended. The psychometric characteristics of the items were studied as a function of the Bloom's levels addressed, item format, and number of choices in MCQs. RESULTS: Items addressing analysis skills were more difficult. No differences were found between case based and noncase based items in terms of their difficulty, with a slightly better discrimination in the latter. Open-ended items were easier, yet more discriminative. MCQs with higher number of options were easier. Open-ended questions were significantly more discriminative in comparison to MCQs as case based items while they were more discriminative as noncase based items. CONCLUSION: Item formats, structure, and number of options in MCQs significantly affected the psychometric properties of the studied items. Noncase based items and open-ended items were easier and more discriminative than case based items and MCQs, respectively. Examination items should be prepared considering the above characteristics to improve their psychometric properties and maximize their usefulness.

Prevalence, determinants, and characteristics of extemporaneous compounding in Jordanian pharmacies.

BACKGROUND: Pharmaceutical compounding is an essential component in pharmacy practice allowing pharmacists to provide dosage forms or strengths that are commercially unavailable. Medications compounded for patient-specific needs contribute to personalized medicine. Extemporaneous compounding provided by pharmacies overcomes the market shortage of these therapeutic products. The aim of this study is to investigate and characterize the prevalence, characteristics, and determinants of extemporaneous compounding in Jordanian pharmacies. METHODS: This study was based on a cross-sectional questionnaire and included 431 randomly selected pharmacies in the twelve governorates of the country. Data were collected via face to face interviews of pharmacists who voluntarily and verbally responded to the questions. RESULTS: Results revealed that 223 (51.7%) of the surveyed pharmacies practiced extemporaneous compounding. The main reason for not providing extemporaneous compounding services was lack of prescription orders for compounded preparations (53.8%). The second reason was lack of the equipment and supplies necessary for compounding (24.4%). Extemporaneous compounding prescriptions were mainly issued by dermatologists (98.2%); dermatological indication was the most common of all extemporaneous compounded prescriptions. The main reason for requesting compounded medications was the lack of a commercially available product (87.9%). The vast majority of the compounded dosage forms were creams (99.6) and ointments (91.5), followed by solutions (23.3%). Only 5 (2.2%) of the studied compounding pharmacies prepared sterile products. The major sources for compounding protocols were the physician order (94.2%), and 'in-house' protocols (44.8%). However, the main resource for estimating compounded medications expiration date was information based on pharmacist's experience (57.8%) and the physician's order (53.4%). CONCLUSIONS: Extemporaneous compounding is a common element of pharmaceutical care. Topical preparations are the most commonly compounded products. Finding from this study suggest that there is a need for standardizing the compounded product formularies, product quality testing, and improving the consistency in estimation of an expiration date of compounded products.

Does Salt and Mineral Content of Dead Sea Mud Affect Its Irritation Potential: A Laser Doppler Flowmetry Study.

The aim of the study was to investigate skin microcirculation, flux, and temperature changes induced by the application of Dead Sea mud (DSM) formulas with different mud salts and mineral contents using laser Doppler flowmetry. Instrumental analysis of eight over-the-shelf DSM products and four different samples of nonformulated Dead Sea mud were carried out to determine their contents of various salts and elements, including K, Na, Cl, Mg, Mn, Ca, SO3, SiO2, Al, Br, Fe, Hg, Cr, Co, Ni, Cu, Zn, As, Cd, Pb, and Sr. Three DSM samples with different levels of salts were then used to study the influence of salt content on skin irritation potential using laser Doppler flowmetry. Fifteen healthy nonsmoking females aged 18-45 years participated in the study. Subjects were randomly assigned to either "Salted" mud group (n = 5), "As is" mud group (n = 5), or "Over-the-Shelf" mud group (n = 5). Five circular areas were marked on the ventral aspect of each forearm. One forearm was assigned randomly for mud treatment and the other forearm was untreated. Ten milliliters of mud was applied on the assigned forearm and left for 30 minutes. Two reading protocols were designed and used to study the effects of tested type of mud on skin blood flux and temperature during mud application (protocol 2) as well as before and after mud removal (protocol 1). All types of tested mud were not associated with a significant measurable elevation in skin temperature and skin blood flow. All types of Dead Sea mud did not cause detectable microcirculatory and skin temperature changes regardless of their different mineral and salts contents.

Quantitative analysis of single best answer multiple choice questions in pharmaceutics.

INTRODUCTION: The purpose of this study was to: (1) analyze the quality of single best answer multiple choice questions (MCQs) used in pharmaceutics exams, (2) identify the correlation between difficulty index (DIF I), discriminating index (DI), and distractor efficiency (DE), and (3) understand the relationship between DIF I, DI, and DE and the number of MCQ answer options and their cognitive level. METHODS: 429 MCQs used in pharmaceutics exams were analyzed. The quality of the MCQs was evaluated using DIF I, DI, and DE. The number of answer options and the cognitive level tested by each item were evaluated. Relationships between DIF I, DI, and DE were measured using Pearson's correlations and t-tests. RESULTS: DIF I showed a significant negative correlation with DI within questions that measured information recall. A significant negative correlation between DIF I and DI was observed in questions with four and five answer options regardless of the cognitive level measured. The highest DI values were found in moderate difficulty questions, while the worst DE was observed for the easiest questions. Questions that measured analytical and problem-solving abilities were more difficult than those measuring information recall. Questions with four and five answer options had excellent discrimination. CONCLUSIONS: Single best answer MCQs are a valuable assessment tool capable of evaluating higher cognitive skills. Significant correlation between DIF I and DI can indicate the examination quality. Higher quality MCQs are constructed using four and five answer options.

The influence of ethanol on superdisintegrants and on tablets disintegration.

Disintegration of immediate release tablets originates from the volume expansion of disintegrants within the formulation. Here, we study the impact of ethanol on the disintegrant expansion and on tablets disintegration. The three most commonly used superdisintegrants, namely sodium starch glycolate (SSG), crospovidone (PVPP) and croscarmellose sodium (CCS) were investigated alone and incorporated in dicalcium phosphate and in drug-containing tablets. High (i.e. 40%), but not moderate (i.e. 10%), aqueous ethanol concentrations reduce the size expansion of the three disintegrants compared to water. This "ethanol effect" is the greatest for SSG, followed by CCS and then PVPP. Moreover, the presence of ethanol in the media can significantly influence the disintegration time of drug-containing tablets via affecting both the disintegrant action itself and the drug solubility. For example, the disintegration time of theophylline tablets containing SSG is 8.1-fold greater in 40% aqueous ethanol compared to water. Overall, this study brought to light the existence of a potentially significant interference of alcohol with the disintegration phenomenon, suggesting that the concomitant administration of tablets and intake of alcoholic beverages may affect, in some cases, tablets disintegration. More studies are now needed to verify the importance of the "ethanol effect" on disintegration of commercial dosage forms. Our findings also suggest that PVPP is the disintegrant that is the least affected by alcohol.

Clarithromycin laurate salt: physicochemical properties and pharmacokinetics after oral administration in humans.

OBJECTIVE: To prepare and characterize the physicochemical and pharmacokinetic properties of clarithromycin laurate (CLM-L), a fatty acid salt of clarithromycin (CLM). METHODS: CLM-L was prepared by a simple co-melting process. The formation of CLM-L was confirmed using FTIR, 1H NMR, and 13C NMR. Solubility, intrinsic dissolution rate (IDR), and partitioning properties of CLM-L were determined and compared to those of CLM. Bioavailability of CLM from CLM-L tablets was evaluated in healthy volunteers and compared to immediate release CLM tablets. RESULTS: CLM-L showed lower aqueous solubility, higher partitioning coefficient, and slower dissolution rate. Tablets of CLM-L also showed a significantly slower in vitro release in comparison to CLM tablets. Cmax, Tmax and AUC0→∞ of CLM-L tablets and immediate release CLM tablets did not show a significant difference. However, the AUC0→∞ for the CLM-L tablets tended to be higher than that of CLM tablets at all-time points. CONCLUSION: CLM-L was successfully prepared and its formation was confirmed. CLM-L was more hydrophobic than CLM. It exhibited a slight in vivo absorption enhancement in comparison to CLM. However, its pharmacokinetic behavior was comparable to that of CLM.

Zein as a Pharmaceutical Excipient in Oral Solid Dosage Forms: State of the Art and Future Perspectives.

Zein is the main storage protein of corn and it has several industrial applications. Mainly in the last 10-15 years, zein has emerged as a potential pharmaceutical excipient with unique features. Zein is a natural, biocompatible and biodegradable material produced from renewable sources. It is insoluble, yet due to its amphiphilic nature, it has self-assembling properties, which have been exploited for the formation of micromicroparticle and nanoparticle and films. Moreover, zein can hydrate so it has been used in swellable matrices for controlled drug release. Other pharmaceutical applications of zein in oral drug delivery include its incorporation in solid dispersions of poorly soluble drugs and in colonic drug delivery systems. This review describes the features of zein significant for its use as a pharmaceutical excipient for oral drug delivery, and it summaries the literature relevant to macroscopic zein-based oral dosage forms, i.e. tablets, capsules, beads and powders. Particular attention is paid to the most novel formulations and applications of zein. Moreover, gaps of knowledge as well as possible venues for future investigations on zein are highlighted.

Aggregation of zein in aqueous ethanol dispersions: Effect on cast film properties.

In this study, we evaluate the influence of zein aggregation in aqueous ethanol dispersions on the properties of zein films. The effects of zein concentration, ethanol content and temperature on transmittance of zein dispersions were investigated. Dynamic light scattering was used to measure the degree of zein aggregation in the dispersions. The results indicate that particle size of zein increased with higher zein concentration, lower ethanol level and at lower temperatures. Zein films were prepared by casting from 70% and 90% aqueous ethanol dispersions at different drying temperatures and were evaluated for appearance, thermomechanical and mechanical properties. Higher ethanol levels and higher drying temperatures promoted the formation of more homogenous films. Films made from higher ethanol dispersions had lower glass transition temperatures than those made from lower ethanol dispersions. Moreover, the fragility factor classified the films as strong systems. Mechanical properties of films were measured at different drying temperatures. Stiffer and more resistant films were developed as the drying temperature increased. In conclusion, film properties can be tailored by controlling the composition of the film casting solvent and the drying temperature. Differences in film properties were found to relate to differences in initial degree of aggregation of zein dispersions.

Development of a biphasic dissolution test for Deferasirox dispersible tablets and its application in establishing an in vitro-in vivo correlation.

In a biphasic dissolution medium, the integration of the in vitro dissolution of a drug in an aqueous phase and its subsequent partitioning into an organic phase is hypothesized to simulate the in vivo drug absorption. Such a methodology is expected to improve the probability of achieving a successful in vitro-in vivo correlation. Dissolution of Dispersible tablets of Deferasirox, a biopharmaceutics classification system type II compound, was studied in a biphasic dissolution medium using a flow-through dissolution apparatus coupled to a paddle apparatus. The experimental parameters associated with dissolution were optimized to discriminate between Deferasirox dispersible tablets of different formulations. The dissolution profiles obtained from this system were subsequently used to construct a level A in vitro-in vivo correlation.

Optimization of pH-independent chronotherapeutic release of verapamil HCl from three-layer matrix tablets.

The aim of this work was to evaluate and optimize formulation of three-layer matrix tablets based on xanthan gum (XG) and sodium alginate for chronotherapeutic pH-independent release of verapamil HCl (VH). Artificial neural networks (ANN) were applied in the optimization and compared with multiple linear regression (MLR). A face-centered central composite experimental design was employed with three factors (mass fraction of VH in intermediate layer, X1, and of XG in matrix former of intermediate and outer layers, X2 and X3). The prepared tablets were tested for in vitro release in 0.1 N HCl and phosphate buffer (pH 7.5), tensile strength and friability. Furthermore, swelling observation and release modeling to Weibull function and power law equation of Peppas were employed to help further understanding of release behavior and mechanism. The releases (%) in phosphate buffer (pH 7.5) at 6, 12 and 24 h were selected as responses to depict the mode of release and similarity factor (f2), between release profiles in 0.1N HCl and pH 7.5 during the first 8 h, as response of pH-independence. A desirability function combining the four responses was constructed and overall desirability values were used for the ANN and MLR modeling. Five additional checkpoint formulations, within the experimental domain, were used to validate the external predictability of the models. The constructed ANN model fitted better to the overall desirability than the MLR model (R=0.838 vs. 0.670, for the additional checkpoint formulations) and therefore, was used for prediction of formulation with optimal in vitro drug release.

Effect of formulation variables on the physical properties and stability of Dead Sea mud masks.

The physical stability of Dead Sea mud mask formulations under different conditions and their rheological properties were evaluated as a function of the type and level of thickeners, level of the humectant, incorporation of ethanol, and mode of mud treatment. Formulations were evaluated in terms of visual appearance, pH, moisture content, spreadability, extrudability, separation, rate of drying at 32 degrees C, and rheological properties. Prepared mud formulations and over-the-shelf products showed viscoplastic shear thinning behavior; satisfactory rheological behavior was observed with formulations containing a total concentration of thickeners less than 10% (w/w). Casson and Herschel-Bulkley models were found the most suitable to describe the rheological data of the prepared formulations. Thickener incorporation decreased phase separation and improved formulation stability. Bentonite incorporation in the mud prevented color changes during stability studies while glycerin improved spreadability. Addition of 5% (w/w) ethanol improved mud extrudability, slightly increased percent separation, accelerated drying at 32 degrees C, and decreased viscosity and yield stress values. Different mud treatment techniques did not cause a clear behavioral change in the final mud preparation. B10G and K5B5G were labeled as "best formulas" based on having satisfactory physical and aesthetic criteria investigated in this study, while other formulations failed in one or more of the tests we have performed.

Colloidal stability of citrate and mercaptoacetic acid capped gold nanoparticles upon lyophilization: effect of capping ligand attachment and type of cryoprotectants.

For various applications of gold nanotechnology, long-term nanoparticle stability in solution is a major challenge. Lyophilization (freeze-drying) is a widely used process to convert labile protein and various colloidal systems into powder for improved long-term stability. However, the lyophilization process itself may induce various stresses resulting in nanoparticle aggregation. Despite a plethora of studies evaluating lyophilization of proteins, liposomes, and polymeric nanoparticles, little is known about the stability of gold nanoparticles (GNPs) upon lyophilization. Herein, the effects of lyophilization and freeze-thaw cycles on the stability of two types of GNPs: Citrate-capped GNPs (stabilized via weakly physisorbed citrate ions, Cit-GNPs) and mercaptoacetic acid-capped GNPs (stabilized via strongly chemisorbed mercaptoacetic acid, MAA-GNPs) are investigated. Both types of GNPs have similar core size and effective surface charge as evident from transmission electron microscopy and zeta potential measurements, respectively. Plasmon absorption of GNPs and its dependence on nanoparticle aggregation was employed to follow stability of GNPs in combination with dynamic light scattering analysis. Plasmon peak broadening index (PPBI) is proposed herein for the first time to quantify GNPs aggregation using nonlinear Gaussian fitting of GNPs UV-vis spectra. Our results indicate that Cit-GNPs aggregate irreversibly upon freeze-thaw cycles and lyophilization. In contrast, MAA-GNPs exhibits remarkable stability under the same conditions. Cit-GNPs exhibit no significant aggregation in the presence of cryoprotectants (molecules that are typically used to protect labile ingredients during lyophilization) upon freeze-thaw cycles and lyophilization. The effectiveness of the cyroprotectants evaluated was on the order of trehalose or sucrose > sorbitol > mannitol. The ability of cryoprotectants to prevent GNPs aggregation was dependent on their chemical structure and their ability to interact with the GNPs as assessed with zeta potential analysis.

Application of active layering and coating techniques in the development of a multiparticulate, controlled release dosage form of a high-dose, highly soluble drug.

CONTEXT: The success of the development of controlled release, multilayered, multiparticulate dosage form of a high-dose, highly-soluble drug is dependent upon proper material and processing choices. OBJECTIVE: To develop a controlled release dosage form of diltiazem hydrochloride using active layering and coating. METHODS: Active layering was achieved by spraying a drug solution onto sugar cores using polyvinyl alcohol - polyethylene glycol as a binder. Layered pellets with highest loading and lowest binder content were coated using aqueous dispersions of polyvinyl acetate (PVAc). The effects of the plasticizer and curing on drug release were evaluated. RESULTS AND DISCUSSION: The binder level had no effect on the process efficiency. Drug release from PVAc-coated pellets was slowed by increasing PVAc level. Plasticization slowed drug release in comparison to nonplasticized formulations. Curing affected drug release of nonplasticized formulations only. Protection against humidity was essential in stabilizing drug release under stability study conditions. CONCLUSION: Materials and process used were suitable to face the challenge posed by the high dose of the water-soluble drug on the success of the formulation. The effects of the plasticizer, curing and ability of packaging to protect against elevated humidity on the performance of the studied system should be considered in development.

Construction, in vitro and in vivo evaluation of an in-house conductance meter for measurement of skin hydration.

Different probes are used in dermato-cosmetic research to measure the electrical properties of the skin. The principle governing the choice of the geometry and material of the measuring probe is not well defined in the literature and some device's measuring principles are not accessible for the scientific community. The purpose of this work was to develop a simple inexpensive conductance meter for the objective in vivo evaluation of skin hydration. The conductance meter probe was designed using the basic equation governing wave propagation along Transverse Electromagnetic transmission lines. It consisted of two concentric copper circular electrodes printed on FR4 dielectric material. The performance of the probe was validated by evaluating its measurement depth, its ability to monitor in vitro water sorption-desorption and in vivo skin hydration effect in comparison to that of the Corneometer CM 825. The measurement depth of the probe, 15 µm, was comparable to that of CM 825. The in vitro readings of the probe correlated strongly with the amount of water adsorbed on filter paper. Skin hydration after application of a moisturizer was monitored effectively by the new probe with good correlation to the results of CM 825. In conclusion, a simple probe for evaluating skin hydration was made from off-the-shelf materials and its performance was validated in comparison to a commercially available probe.

Evaluation of hydrophilic matrix tablets based on Carbopol(®) 971P and low-viscosity sodium alginate for pH-independent controlled drug release.

BACKGROUND: The aim of this study was to evaluate matrix tablets containing different ratios of Carbopol(®) 971P (CP) to low-viscosity sodium alginate (SA) and assess their suitability for pH-independent controlled drug release. METHODS: Two processing methods (physical mixing, PM and spray-drying, SD) were applied before compaction and the release from corresponding matrices was compared. The release from CP-SA PM matrices was also investigated using three model drugs (paracetamol, salicylic acid, and verapamil HCl) and two dissolution media (0.1 N HCl or phosphate buffer, pH = 6.8), and the release rate, mechanism, and pH-dependence were characterized by fitting of Higuchi and Peppas models, and evaluation of similarity factor. Furthermore, swelling behavior of CP-SA matrix tablets was studied for evaluating its impact on drug release. RESULTS: The processing method (SD or PM) markedly affected the drug release from CP-SA matrices. ANOVA tests showed significant effects of the CP:SA ratio and drug type on the release rate (expressed by the constant, K(H), from Higuchi model) and of the dissolution medium on the release mechanism (expressed by the exponent, n, from Peppas model). Similarity factor (f2) indicated that the CP:SA ratios ≥ 25:75 and ≥ 50:50 were suitable for pH-independent release of paracetamol and salicylic acid, respectively, although for verapamil HCl, the matrix with low CP:SA ratio (0:100) showed remarkably reduced pH-dependence of release. Swelling parameters (water uptake and mass loss) were significantly changed with experimental variables (CP:SA ratio, medium, and time) and were in good correlation with drug release. CONCLUSION: Matrix tablets based on CP and SA form a potentially useful versatile system for pH-independent controlled drug release.

Pancreatic lipase inhibition activity of trilactone terpenes of Ginkgo biloba.

The prevalence of obesity is increasing at an alarming rate, but, unfortunately, only a few drugs are currently available on the market. In the present study, the methanolic extract of Ginkgo biloba L. (Ginkgoaceae) was investigated as an inhibitor of pancreatic lipase (PL) in an attempt to explain its hypolipidaemic activity. In vitro assay of G. biloba leaves extract revealed a substantial PL inhibition activity (IC(50) = 16.5 µg/mL). Further investigation was performed by employing theoretical docking simulations and experimental testing to uncover the active constituents responsible for G. biloba anti-lipase activity. Virtually, terpene trilactones, including ginkgolides and bilobalide, were found to fit within the binding pocket of PL via several attractive interactions with key amino acids. Experimentally, ginkgolides A, B, and bilobalide were found to inhibit PL significantly (IC(50) = 22.9, 90.0, and 60.1 µg/mL, respectively). Our findings demonstrated that the hypolipidaemic effects of G. biloba extract can be attributed to the inhibition of PL by, at least in part, terpene trilactones. In conclusion, this work can be considered a new step towards the discovery of new natural safe hypolipidaemic PL inhibitors.