AAPS PharmSci

Publications in this journal

• Article: Carrageenan based freeze-dried wafers incorporating paracetamol and indomethacin for mucosal drug delivery

  Kianfar F, Chowdhry B, Antonijevic M, Boateng J
  AAPS PharmSci 01/2011; 13(S2):R6212.
• Article: Taste masking of bitter APIs by using hot melt extrusion (HME)

  Maniruzzaman M, Boateng J, Douroumis D
  AAPS PharmSci 01/2011; 13(S2):3273.
• Article: Formulation and evaluation of lyophilised thiolated chitosan wafers for buccal mucosal delivery of protein

  Ayensu I, Mitchelll J, Boateng JS
  AAPS PharmSci 01/2011; 13(S2):M1144.
• Article: 17. Monica Rao, Anuradha Ranpise, Sameer Borate, Kaushik Thanki. Mechanistic Evaluation of the effect of sintering on Compritol 888 ATO matrices. AAPS Pharm SciTech. 2009, DOI: 10.1208/s12249-009-9211-8.

  Monica Rao, Anuradha Ranpise, Sameer Borate, Kaushik Thanki
  AAPS PharmSci 01/2009;
• Source

  Available from: aapsj.org

  Article: Assessment of fertility in male rats after extended chemical castration with a GnRH antagonist.

  Susan S D'Souza, Francesca Selmin, Santos B Murty, Wei Qiu, B C Thanoo, Patrick P DeLuca
  [show abstract] [hide abstract]
  ABSTRACT: The purpose of this study was to assess whether male rats whose testosterone levels were suppressed to castration levels (<0.5 ng/mL) for a 1-year period by the sustained delivery of orntide acetate, a GnRH antagonist, would return to fertility (ie, produce offspring) after serum testosterone returned to control levels. Male rats comprising a treatment group (orntide microspheres, dose = 27 mg/kg/y), a vehicle control group, and a control group of proven male breeders were used. For the treatment and vehicle control groups, serum orntide and testosterone levels were monitored at periodic intervals for 14 months from the initiation of treatment. After serum testosterone levels returned to vehicle control levels and orntide serum levels were no longer discernible for the treated group, each of the animals was housed with 2 drug-naive, female, proven breeders. All the breeder females produced offspring with the exception of 1 female housed with a male rat from the treatment group and the 2 females housed with a single male rat from the vehicle control group. The mean size and weight of the litters from each group were not statistically different. Further, fertility of the offspring from each group was assessed. The male and female offspring studied were all shown to be fertile. The results suggest that lack of fertility due to testosterone suppression in male rats is reversible after cessation of treatment with the GnRH analog, orntide.
  AAPS PharmSci 04/2004; 6(1):E10.
• Source

  Available from: aapsj.org

  Article: Beta-cyclodextrin complexes of celecoxib: molecular-modeling, characterization, and dissolution studies.

  M Narender Reddy, Tasneem Rehana, S Ramakrishna, K P R Chowdhary, P V Diwan
  [show abstract] [hide abstract]
  ABSTRACT: Celecoxib, a specific inhibitor of cycloxygenase-2 (COX-2) is a poorly water-soluble nonsteroidal anti-inflammatory drug with relatively low bioavailability. The effect of beta-cyclodextrin on the aqueous solubility and dissolution rate of celecoxib was investigated. The possibility of molecular arrangement of inclusion complexes of celecoxib and beta-cyclodextrin were studied using molecular modeling and structural designing. The results offer a better correlation in terms of orientation of celecoxib inside the cyclodextrin cavity. Phase-solubility profile indicated that the solubility of celecoxib was significantly increased in the presence of beta-cyclodextrin and was classified as A(L)-type, indicating the 1:1 stoichiometric inclusion complexes. Solid complexes prepared by freeze drying, evaporation, and kneading methods were characterized using differential scanning calorimetry, powder x-ray diffractometry, and scanning electron microscopy. In vitro studies showed that the solubility and dissolution rate of celecoxib were significantly improved by complexation with beta-cyclodextrin with respect to the drug alone. In contrast, freeze-dried complexes showed higher dissolution rate than the other complexes.
  AAPS PharmSci 04/2004; 6(1):E7.
• Article: Preparation, characterization, and biodistribution study of technetium-99m -labeled leuprolide acetate-loaded liposomes in Ehrlich ascites tumor-bearing mice.

  N Arulsudar, N Subramanian, P Mishra, K Chuttani, R K Sharma, R S R Murthy
  [show abstract] [hide abstract]
  ABSTRACT: The purpose of this study was to prepare conventional and sterically stabilized liposomes containing leuprolide acetate in an attempt to prolong the biological half life of the drug, to reduce the uptake by reticuloendothelial system (RES), and to reduce the injection frequency of intravenously administered peptide drugs. The conventional and sterically stabilized liposomes containing leuprolide acetate were prepared by reverse phase evaporation method and characterized for entrapment efficiency and particle size. Radiolabeling of leuprolide acetate and its liposomes was performed by direct labeling with reduced technetium-99m. Its biodistribution and imaging characteristics were studied in ehrlich ascites tumor (EAT)-bearing mice after labeling with technetium-99m. The systemic pharmacokinetic studies were performed in rabbits. A high uptake by tumor was observed by sterically stabilized liposome containing leuprolide acetate compared with free drug and conventional liposomes. The liver/tumor uptake ratio of free drug, conventional (LL), and sterically stabilized liposomes (SLL5000 and SLL2000) was found to be 20, 7.99, 1.63, and 1.23, respectively, which showed the increased accumulation of sterically stabilized liposomes in tumor compared with the free drug and conventional liposomes at 24 hours postinjection. Liver uptake of sterically stabilized liposomes was still 7-fold less than the conventional liposomes. The marked accumulation of liposomes in the tumor-bearing mice was also documented by gamma scintigraphic studies. The findings demonstrate the distribution of these liposomes within solid tumor and prove that the sterically stabilized liposomes experience increased tumor uptake and prolonged circulation half life. Hence these findings will be relevant for the optimal design of long circulating liposomes for the peptide drugs and for targeting of liposomes toward tumor.
  AAPS PharmSci 03/2004; 6(1):E5.
• Article: Evaluation of a new coprocessed compound based on lactose and maize starch for tablet formulation.

  Karsten Hauschild, Katharina M Picker-Freyer
  [show abstract] [hide abstract]
  ABSTRACT: The development of new direct compression excipients should include a comprehensive and rapid determination of deformation properties. The aim of this study was to characterize StarLac, a new coprocessed compound for direct compression based on lactose and maize starch. For this purpose, the effects of the base materials (maize starch and spray-dried lactose) were considered and the influence of the spray-drying process was investigated. This was performed by comparing the physical mixture of starch and spray-dried lactose at the same ratio as for StarLac. For analysis of the deformation behavior, the 3-D model and the Walker equation were applied; for verification, the Heckel equation and the pressure time function (a modified Weibull equation) were used. The advantages of StarLac are its good flowability depending on the spray-drying process, an acceptable crushing force due to its lactose content, its rapid disintegration depending on starch, and a brilliant fast release of an active ingredient, such as theophylline monohydrate. The volume-pressure deformation properties of StarLac were dependent on the lactose properties. Only at high maximum relative density (rho(rel, max)) did the influence of starch cause a change in these properties. A network-like structure can be observed using scanning electron microscopy pictures. Overall, StarLac deformed plastically with a low portion of elasticity. The physical mixture exhibited a more elastic behavior than StarLac. However, the part of the powder that was irreversibly compressed was much lower than was observed for the single substances. This behavior is caused by an interaction between the components, which in StarLac is prevented by spray drying.
  AAPS PharmSci 02/2004; 6(2):e16.
• Source

  Available from: aapsj.org

  Article: A photo-crosslinked poly(vinyl alcohol) hydrogel growth factor release vehicle for wound healing applications.

  Sharon L Bourke, Mohammad Al-Khalili, Tonye Briggs, Bozena B Michniak, Joachim Kohn, Laura A Poole-Warren
  [show abstract] [hide abstract]
  ABSTRACT: The objective of this study was to develop and evaluate a hydrogel vehicle for sustained release of growth factors for wound healing applications. Hydrogels were fabricated using ultraviolet photo-crosslinking of acrylamide-functionalized nondegradable poly(vinyl alcohol) (PVA). Protein permeability was initially assessed using trypsin inhibitor (TI), a 21 000 MW model protein drug. TI permeability was altered by changing the solids content of the gel and by adding hydrophilic PVA fillers. As the PVA content increased from 10% to 20%, protein flux decreased, with no TI permeating through 20% PVA hydrogels. Further increase in model drug release was achieved by incorporating hydrophilic PVA fillers into the hydrogel. As filler molecular weight increased, TI flux increased. The mechanism for this is most likely an alteration in protein/gel interactions and transient variations in water content. The percent protein released was also altered by varying protein loading concentration. Release studies conducted using growth factor in vehicles with hydrophilic filler showed sustained release of platelet-derived growth factor (PDGF-beta,beta) for up to 3 days compared with less than 24 hours in the controls. In vitro bioactivity was demonstrated by doubling of normal human dermal fibroblast numbers when exposed to growth factor-loaded vehicle compared to control. The release vehicle developed in this study uses a rapid and simple fabrication method, and protein release can be tailored by modifying solid content, incorporating biocompatible hydrophilic fillers, and varying protein loading concentration.
  AAPS PharmSci 01/2004; 5(4):E33.
• Article: Lipid-based supramolecular systems for topical application: a preformulatory study.

  Elisabetta Esposito, Nadia Eblovi, Silvia Rasi, Markus Drechsler, Giordano M Di Gregorio, Enea Menegatti, Rita Cortesi
  [show abstract] [hide abstract]
  ABSTRACT: This article describes the production and characterization of monoglyceride-based supramolecular systems by a simple processing technique, avoiding time-consuming procedures, high energy input, and the use of organic solvents. A preformulatory study was performed to study the influence of the experimental parameters on the production of monoglyceride-based disperse systems. In particular the effects of (1) stirring speed, (2) type and concentration of monoglyceride mixture, and (3) type and concentration of surfactant were investigated on the recovery, fraction of larger particles, mean diameter, and shape of smaller particles (so called nanosomes). Dispersions were first characterized by optical microscopy and freeze-fracture electron microscopy. The mean diameter of standard nanosomes, analyzed by photon correlation spectroscopy (PCS) after elimination of larger particles by filtration, was 193.5 nm. Cryotransmission electron microscopy studies, conducted in order to investigate the structure of dispersions, showed the coexistence of vesicles and particles characterized by a cubic organization. X-ray diffraction data revealed the coexistence of 2 different cubic phases, the first being a bicontinuous cubic phase of spatial symmetry Im3m (Q229) and the second belonging to the Pn3m spatial symmetry. A study on the stability of monoglyceride-based dispersions based on macroscopical analysis of organoleptic properties and dimensional analysis by time was performed after elimination of larger particles by filtration. Organoleptic and morphological features do not change by time, appearing free from phase-separation phenomena for almost 1 year from production. PCS studies showed that nanosomes undergo an initial increase in mean diameter within the first month following production; afterwards they generally maintain their dimensions for the next 4 months.
  AAPS PharmSci 12/2003; 5(4):E30.
• Source

  Available from: aapsj.org

  Article: Pharmacogenomics of multigenic diseases: sex-specific differences in disease and treatment outcome.

  Julia Pinsonneault, Wolfgang Sadée
  [show abstract] [hide abstract]
  ABSTRACT: Numerous genetic variations have been shown to affect disease susceptibility and drug response. Pharmacogenomics aims at improving therapy on the basis of genetic information for each individual patient. Furthermore, sex chromosomes broadly determine biological differences between males and females. Consequently, substantial sex differences exist in phenotypic manifestation of disease and treatment response. This review discusses the role of sex in coronary artery disease, schizophrenia, and depression--complex multigenic disorders with considerable sex differences in frequency and presentation. Moreover, genetic factors underlying disease and drug response appear to differ between male and female patients. This appears to result at least in part from different physiological effects exerted by sex hormones such that polymorphisms in susceptibility genes may have physiological relevance only in males or females. However, few examples have been discovered to play a role in complex multigenic diseases, and the mechanistic basis of genetic variants as sex-dependent susceptibility factors has yet to be explored. Therefore, pharmacogenomic studies must consider sex differences in an effort to optimize individual drug therapy.
  AAPS PharmSci 12/2003; 5(4):E29.
• Source

  Available from: aapsj.org

  Article: Hydroxyzine from topical phospholipid liposomal formulations: evaluation of peripheral antihistaminic activity and systemic absorption in a rabbit model.

  Abeer A W Elzainy, Xiaochen Gu, F Estelle R Simons, Keith J Simons
  [show abstract] [hide abstract]
  ABSTRACT: Hydroxyzine, an effective but sedating H1-antihistamine is given orally to treat allergic skin disorders. This study was performed to assess the peripheral H(1)-antihistaminic activity and extent of systemic absorption of hydroxyzine from liposomes applied to the skin. Using L-alpha-phosphatidylcholine (PC), small unilamellar vesicles (SUVs) and multilamellar vesicles (MLVs) containing hydroxyzine were prepared. Hydroxyzine in Glaxal Base (GB) was used as the control. Using a randomized, crossover design, each formulation, containing 10 mg of hydroxyzine, was applied to the shaved backs of 6 rabbits (3.08 +/- 0.05 kg). Histamine-induced wheal tests and blood sampling were performed at designated time intervals up to 24 hours. Compared with baseline, hydroxyzine from all formulations significantly suppressed histamine-induced wheal formation by 75% to 95% for up to 24 hours. Mean maximum suppression, 85% to 94%, occurred from 2 to 6 hours, with no differences among the formulations. The areas of plasma hydroxyzine concentration versus time area under the curve (AUCs) from PC-SUV and PC-MLV, 80.1 +/- 20.8 and 78.4 +/- 33.9 ng/mL/h, respectively, were lower than that from GB, 492 +/- 141 ng/mL/h (P < or =.05) over 24 hours. Plasma concentrations of cetirizine arising in-vivo as the active metabolite of hydroxyzine, from PC-SUV, PC-MLV, and GB, were similar with AUCs of 765 +/- 50, 1035 +/- 202, and 957 +/- 227 ng/mL/h, respectively (P < or =.05). Only 0.02% to 0.06% of the initial hydroxyzine dose remained on the skin after 24 hours. In this model, hydroxyzine from SUV and MLV had excellent topical H1-antihistaminic activity, and minimal systemic exposure occurred. Cetirizine formed in-vivo contributed to some of H1-antihistaminic activity.
  AAPS PharmSci 11/2003; 5(4):E28.
• Source

  Available from: aapsj.org

  Article: Amphiphilic star-like macromolecules as novel carriers for topical delivery of nonsteroidal anti-inflammatory drugs.

  Jelena Djordjevic, Bozena Michniak, Kathryn E Uhrich
  [show abstract] [hide abstract]
  ABSTRACT: The objective of this study was to evaluate amphiphilic star-like macromolecules (ASMs) as a topical drug delivery system. Indomethacin, piroxicam, and ketoprofen were individually encapsulated into the ASMs using coprecipitation. The effects of the ASMs on percutaneous permeation of nonsteroidal anti-inflammatory drugs (NSAIDs) across full thickness, hairless mouse skin were evaluated in vitro using modified Franz diffusion cells. In addition, solubility and in vitro release experiments were performed to characterize ASMs behavior in aqueous media. Poly(ethylene glycol) (PEG) and Pluronic P-85 were used as polymer controls to compare the role of PEG and amphiphilic behavior in the ASMs. In vitro release experiments indicated that ASMs can delay drug release (P <.05), whereas solubility measurements showed that ASMs can increase NSAIDs aqueous solubility (P <.05). Percutaneous permeation studies revealed that ASMs decreased both flux and Q24 of drugs compared with the control (P <.10). Skin pretreatment studies with ASM-containing solution before drug application demonstrated that pretreatment similarly influenced NSAID percutaneous permeation. In conclusion, ASMs likely slow drug permeation through 2 mechanisms, delayed drug diffusion from its core and skin dehydration by its shell. Thus, ASMs may be useful for delayed dermal delivery or prevention of compound permeation through the skin (eg, sunscreens, N,N-diethyl-m-toluamide [DEET]) from aqueous formulations.
  AAPS PharmSci 10/2003; 5(4):E26.
• Source

  Available from: aapsj.org

  Article: Evaluation of sucrose esters as alternative surfactants in microencapsulation of proteins by the solvent evaporation method.

  Bi-Botti C Youan, Alamdar Hussain, Nga T Nguyen
  [show abstract] [hide abstract]
  ABSTRACT: Sucrose esters (SE) are surfactants with potential pharmaceutical applications because of their low toxicity, biocompatibility, and excellent biodegradability. The objective of the study was to investigate SE as alternative surfactants in stabilizing emulsions for the preparation of protein-loaded microparticles. To achieve this goal, using bovine serum albumin as model protein and 75/25 poly(d,l-lactide-co-glycolide) as polymer carrier, we have investigated the influence of the following formulation variables on particle characteristics: (1) SE concentration from 0.01% to 1% (wt/vol), (2) hydrophile-lipophile balance (HLB) value of SE from 6 to 15, and (3) the nature of emulsion stabilizer. The formulations were characterized using ATR-FTIR spectroscopy, bicinchoninic acid protein assay, optical microscopy and SDS-PAGE. Results showed that at 0.05% (wt/vol) surfactant concentration, SE with HLB of 6 to 15 provided discrete and spherical microparticles with the highest encapsulation efficiency compared with controls polyvinyl alcohol (PVA) and poloxamer 188. These results may be explained by the difference in critical micelle concentration, diffusion, and partition coefficient among the tested surfactants. HLB values were consistent with SE spectral data. The protein molecular weight was preserved after the encapsulation process. The effective SE concentration was far less (20- to 200-fold) than that is usually required for PVA in microencapsulation of proteins. However, the encapsulation efficiency was relatively lower (approximately 13.5%). These preliminary results suggest that it may be desirable to optimize such formulations in vitro and in vivo for SE to be eventually used as alternative surfactants in the development of microparticulate systems for parenteral delivery of protein and gene medicines.
  AAPS PharmSci 02/2003; 5(2):E22.