Displaying publications 81 - 100 of 234 in total

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  1. Effect of permeation enhancers in the mucoadhesive buccal patches of salbutamol sulphate for unidirectional buccal drug delivery
    Prasanth VV, Puratchikody A, Mathew ST, Ashok KB
    Res Pharm Sci, 2014 Jul-Aug;9(4):259-68.
    PMID: 25657797
    The purpose of this work was to study the effect of various permeation enhancers on the permeation of salbutamol sulphate (SS) buccal patches through buccal mucosa in order to improve the bioavailability by avoiding the first pass metabolism in the liver and possibly in the gut wall and also achieve a better therapeutic effect. The influence of various permeation enhancers, such as dimethyl sulfoxide (DMSO), linoleic acid (LA), isopropyl myristate (IPM) and oleic acid (OA) on the buccal absorption of SS from buccal patches containing different polymeric combinations such as hydroxypropyl methyl cellulose (HPMC), carbopol, polyvinyl alcohol (PVA), polyvinyl pyrollidone (PVP), sodium carboxymethyl cellulose (NaCMC), acid and water soluble chitosan (CHAS and CHWS) and Eudragit-L100 (EU-L100) was investigated. OA was the most efficient permeation enhancer increasing the flux greater than 8-fold compared with patches without permeation enhancer in HPMC based buccal patches when PEG-400 was used as the plasticizer. LA also exhibited a better permeation enhancing effect of over 4-fold in PVA and HPMC based buccal patches. In PVA based patches, both OA and LA were almost equally effective in improving the SS permeation irrespective of the plasticizer used. DMSO was more effective as a permeation enhancer in HPMC based patches when PG was the plasticizer. IPM showed maximum permeation enhancement of greater than 2-fold when PG was the plasticizer in HPMC based buccal patches.
    Matched MeSH terms: Biological Availability
  2. Simple liquid chromatographic method for the determination of naltrexone in human plasma using amperometric detection
    Peh KK, Billa N, Yuen KH
    J Chromatogr B Biomed Sci Appl, 1997 Nov 07;701(1):140-5.
    PMID: 9389350
    A simple liquid chromatographic method using amperometric detection was developed for the determination of naltrexone in human plasma. Prior to analysis, naltrexone and the internal standard (naloxone) were extracted from plasma samples using a 9:1 mixture of chloroform and isopropyl alcohol. The mobile phase comprised 0.1 M disodium hydrogen orthophosphate (pH 3.5) and acetonitrile (85.5:14.5, v/v). Analysis was run at a flow-rate of 0.8 ml/min with the detector operating under oxidative mode at an applied potential of +0.95 V. The method is specific and sensitive with a detection limit of approximately 1 ng/ml at a signal-to-noise ratio of 3:1. Mean recovery value of the extraction procedure was about 93%, while the within day and between day coefficient of variation and percent error values of the assay method were all less than 10%. The calibration curve was linear over a concentration range of 1.5-100 ng/ml.
    Matched MeSH terms: Biological Availability
  3. Simple high-performance liquid chromatographic method for the determination of acyclovir in human plasma using fluorescence detection
    Peh KK, Yuen KH
    J Chromatogr B Biomed Sci Appl, 1997 May 23;693(1):241-4.
    PMID: 9200543
    A simple high-performance liquid chromatographic method using fluorescence detection was developed for the determination of acyclovir in human plasma. The method entailed direct injection of the plasma sample after deproteination. It is both specific and sensitive with a detection limit of 30 ng/ml at a signal-to-noise ratio of 3:1, and is thus suitable for use in pharmacokinetic studies of acyclovir. The method had a mean absolute recovery of 96%, while the within-day and between-day coefficients of variation and percentages error were all less than 8%. The calibration curve was linear over a concentration range of 62.5-4000 ng/ml.
    Matched MeSH terms: Biological Availability
  4. Comparative bioavailability study of two atenolol tablet preparations
    Peh KK, Yuen KH, Wong JW, Toh WT
    Drug Dev Ind Pharm, 1999 Mar;25(3):357-60.
    PMID: 10071830
    A study was conducted to compare the bioavailability of a generic product of atenolol (Normaten FC) with the innovator product, Tenormin. Twelve healthy adult volunteers participated in the study conducted according to a randomized, two-way crossover design. The preparations were compared using area under the plasma concentration-time curve AUC0-infinity, peak plasma concentration Cmax, and time to reach peak plasma concentration Tmax. No statistically significant difference was obtained between the Tmax values and the logarithmic transformed AUC0-infinity and Cmax values of the two products. Moreover, the 90% confidence interval for the ratio of the logarithmically transformed AUC0-infinity values of Normaten FC over those of Tenormin was found to lie between 0.82 and 0.98, while that of the logarithmically transformed Cmax values was between 0.82 and 1.09, both being within the bioequivalence limit of 0.80-1.25. The values of elimination half-life t1/2 between the two products were also found comparable and not significantly different statistically. The t1/2 values obtained in our study were slightly longer than those reported in the literature for other population groups.
    Matched MeSH terms: Biological Availability
  5. Recent update of toxicity aspects of nanoparticulate systems for drug delivery
    Patnaik S, Gorain B, Padhi S, Choudhury H, Gabr GA, Md S, et al.
    Eur J Pharm Biopharm, 2021 Apr;161:100-119.
    PMID: 33639254 DOI: 10.1016/j.ejpb.2021.02.010
    Potential research outcomes on nanotechnology-based novel drug delivery systems since the past few decades attracted the attention of the researchers to overcome the limitations of conventional deliveries. Apart from possessing enhanced solubility of poorly water-soluble drugs, the targeting potential of the carriers facilitates longer circulation and site-specific delivery of the entrapped therapeutics. The practice of these delivery systems, therefore, helps in maximizing bioavailability, improving pharmacokinetics profile, pharmacodynamics activity and biodistribution of the entrapped drug(s). In addition to focusing on the positive side, evaluation of nanoparticulate systems for toxicity is a crucial parameter for its biomedical applications. Due to the size of nanoparticles, they easily traverse through biological barriers and may be accumulated in the body, where the ingredients incorporated in the formulation development might accumulate and/or produce toxic manifestation, leading to cause severe health hazards. Therefore, the toxic profile of these delivery systems needs to be evaluated at the molecular, cellular, tissue and organ level. This review offers a comprehensive presentation of toxicity aspects of the constituents of nanoparticular based drug delivery systems, which would be beneficial for future researchers to develop nanoparticulate delivery vehicles for the improvement of delivery approaches in a safer way.
    Matched MeSH terms: Biological Availability
  6. Phospholipid Complex Formulation Technology for Improved Drug Delivery in Oncological Settings: a Comprehensive Review
    Patil J, Pawde DM, Bhattacharya S, Srivastava S
    AAPS PharmSciTech, 2024 Apr 25;25(5):91.
    PMID: 38664316 DOI: 10.1208/s12249-024-02813-x
    Addressing poor solubility and permeability issues associated with synthetic drugs and naturally occurring active compounds is crucial for improving bioavailability. This review explores the potential of phospholipid complex formulation technology to overcome these challenges. Phospholipids, as endogenous molecules, offer a viable solution, with drugs complexed with phospholipids demonstrating a similar absorption mechanism. The non-toxic and biodegradable nature of the phospholipid complex positions it as an ideal candidate for drug delivery. This article provides a comprehensive exploration of the mechanisms underlying phospholipid complexes. Special emphasis is placed on the solvent evaporation method, with meticulous scrutiny of formulation aspects such as the phospholipid ratio to the drug and solvent. Characterization techniques are employed to understand structural and functional attributes. Highlighting the adaptability of the phospholipid complex, the review discusses the loading of various nanoformulations and emulsion systems. These strategies aim to enhance drug delivery and efficacy in various malignancies, including breast, liver, lung, cervical, and pancreatic cancers. The broader application of the drug phospholipid complex is showcased, emphasizing its adaptability in diverse oncological settings. The review not only explores the mechanisms and formulation aspects of phospholipid complexes but also provides an overview of key clinical studies and patents. These insights contribute to the intellectual and translational advancements in drug phospholipid complexes.
    Matched MeSH terms: Biological Availability
  7. A Comprehensive Review on the Role of Polymers in Ocular Drug Delivery
    Paramjot, Wadhwa S, Sharma A, Singh SK, Vishwas S, Kumar R, et al.
    Curr Drug Deliv, 2024;21(1):16-37.
    PMID: 36627785 DOI: 10.2174/1567201820666230110140312
    Amongst different routes of drug delivery systems, ophthalmic drug delivery still requires a careful investigation and strict parameter measurements because the eyes are one of the most sensitive parts of the body and require special attention. The conventional systems for eyes lead to rapid elimination of formulation and hence very small contact time on the ocular epithelium. The current review article covers various types of polymers used in ocular drug delivery along with their applications/ limitations. Polymers are widely used by researchers in prodrug techniques and as a penetration enhancer in ocular delivery. This article covers the role and use of different polymeric systems which makes the final formulation a promising candidate for ophthalmic drug delivery. The researchers are still facing multiple challenges in order to maintain the therapeutic concentration of the drug in the eyes because of its complex structure. There are several barriers that further restrict the intraocular entry of the drug. In order to remove/reduce such challenges, these days various types of polymers are used for ocular delivery in order to develop different drug carrier systems for better efficacy and stability. The polymers used are highly helpful in increasing residence time by increasing the viscosity at the ocular epithelium layer. Such preparations also get easily permeated in ocular cells. The combination of different polymeric properties makes the final formulation stable with prolonged retention, high viscosity, high permeability, and better bioavailability, making the final formulation a promising candidate for ocular drug delivery.
    Matched MeSH terms: Biological Availability
  8. Diosgenin, a steroidal saponin, and its analogs: Effective therapies against different chronic diseases
    Parama D, Boruah M, Yachna K, Rana V, Banik K, Harsha C, et al.
    Life Sci, 2020 Nov 01;260:118182.
    PMID: 32781063 DOI: 10.1016/j.lfs.2020.118182
    BACKGROUND: Chronic diseases are a major cause of mortality worldwide, and despite the recent development in treatment modalities, synthetic drugs have continued to show toxic side effects and development of chemoresistance, thereby limiting their application. The use of phytochemicals has gained attention as they show minimal side effects. Diosgenin is one such phytochemical which has gained importance for its efficacy against the life-threatening diseases, such as cardiovascular diseases, cancer, nervous system disorders, asthma, arthritis, diabetes, and many more.

    AIM: To evaluate the literature available on the potential of diosgenin and its analogs in modulating different molecular targets leading to the prevention and treatment of chronic diseases.

    METHOD: A detailed literature search has been carried out on PubMed for gathering information related to the sources, biosynthesis, physicochemical properties, biological activities, pharmacokinetics, bioavailability and toxicity of diosgenin and its analogs.

    KEY FINDINGS: The literature search resulted in many in vitro, in vivo and clinical trials that reported the efficacy of diosgenin and its analogs in modulating important molecular targets and signaling pathways such as PI3K/AKT/mTOR, JAK/STAT, NF-κB, MAPK, etc., which play a crucial role in the development of most of the diseases. Reports have also revealed the safety of the compound and the adaptation of nanotechnological approaches for enhancing its bioavailability and pharmacokinetic properties.

    SIGNIFICANCE: Thus, the review summarizes the efficacy of diosgenin and its analogs for developing as a potent drug against several chronic diseases.

    Matched MeSH terms: Biological Availability
  9. Fulltext Fabrication of Second Generation Smarter PLGA Based Nanocrystal Carriers for Improvement of Drug Delivery and Therapeutic Efficacy of Gliclazide in Type-2 Diabetes Rat Model
    Panda BP, Krishnamoorthy R, Bhattamisra SK, Shivashekaregowda NKH, Seng LB, Patnaik S
    Sci Rep, 2019 11 22;9(1):17331.
    PMID: 31758056 DOI: 10.1038/s41598-019-53996-4
    Drug delivery and therapeutic challenges of gliclazide, a BCS class II drug used in type 2 diabetes mellitus (T2DM) can be overcome by exploring smarter carriers of second-generation nanocrystals (SGNCs). A combined method of emulsion diffusion, high-pressure homogenization and solvent evaporation method were employed in the preparation of gliclazide loaded poly (D, L-lactide-co-glycolide) (PLGA) SGNCs. Taguchi experimental design was adopted in fabrication of Gliclazide SGNc using Gliclazide -PLGA ratio at 1:0.5, 1:0.75, 1:1 with stabilizer (Poloxamer-188, PEG 4000, HPMC E15 at 0.5, 0.75, 1% w/v). The formulated gliclazide of SGNCs were investigated for physicochemical properties, in vitro drug release, and in vivo performance studies using type-2 diabetes rat model. The formulation (SGNCF1) with Drug: PLGA 1: 0.5 ratio with 0.5% w/v Poloxamer-188 produced optimized gliclazide SGNCs. SGNCF1 showed spherical shape, small particle size (106.3 ± 2.69 nm), good zeta potential (-18.2 ± 1.30 mV), small PDI (0.222 ± 0.104) and high entrapment efficiency (86.27 ± 0.222%). The solubility, dissolution rate and bioavailability of gliclazide SGNCs were significantly improved compared to pure gliclazide. The findings emphasize gliclazide SGNCs produce faster release initially, followed by delayed release with improved bioavailability, facilitate efficient delivery of gliclazide in T2DM with better therapeutic effect.
    Matched MeSH terms: Biological Availability
  10. Fulltext Synthesis and Optimization of Chitosan Nanoparticles Loaded with L-Ascorbic Acid and Thymoquinone
    Othman N, Masarudin MJ, Kuen CY, Dasuan NA, Abdullah LC, Md Jamil SNA
    Nanomaterials (Basel), 2018 Nov 07;8(11).
    PMID: 30405074 DOI: 10.3390/nano8110920
    The combination of compounds with different classes (hydrophobic and hydrophilic characters) in single chitosan carrier is a challenge due to the hydrophilicity of chitosan. Utilization of l-ascorbic acid (LAA) and thymoquinone (TQ) compounds as effective antioxidants is marred by poor bioavailability and uptake. Nanoparticles (NPs) solved the problem by functioning as a carrier for them because they have high surface areas for more efficient delivery and uptake by cells. This research, therefore, synthesized chitosan NPs (CNPs) containing LAA and TQ, CNP-LAA-TQ via ionic gelation routes as the preparation is non-toxic. They were characterized using electron microscopy, zetasizer, UV⁻VIS spectrophotometry, and infrared spectroscopy. The optimum CNP-LAA-TQ size produced was 141.5 ± 7.8 nm, with a polydispersity index (PDI) of 0.207 ± 0.013. The encapsulation efficiency of CNP-LAA-TQ was 22.8 ± 3.2% for LAA and 35.6 ± 3.6% for TQ. Combined hydrophilic LAA and hydrophobic TQ proved that a myriad of highly efficacious compounds with poor systemic uptake could be encapsulated together in NP systems to increase their pharmaceutical efficiency, indirectly contributing to the advancement of medical and pharmaceutical sectors.
    Matched MeSH terms: Biological Availability
  11. Fulltext Influence of the Encapsulation Efficiency and Size of Liposome on the Oral Bioavailability of Griseofulvin-Loaded Liposomes
    Ong SG, Ming LC, Lee KS, Yuen KH
    Pharmaceutics, 2016;8(3).
    PMID: 27571096 DOI: 10.3390/pharmaceutics8030025
    The objective of the present study was to investigate the influence of the encapsulation efficiency and size of liposome on the oral bioavailability of griseofulvin-loaded liposomes. Griseofulvin-loaded liposomes with desired characteristics were prepared from pro-liposome using various techniques. To study the effect of encapsulation efficiency, three preparations of griseofulvin, namely, griseofulvin aqueous suspension and two griseofulvin-loaded liposomes with different amounts of griseofulvin encapsulated [i.e., F1 (32%) and F2(98%)], were administered to rats. On the other hand, to study the effect of liposome size, the rats were given three different griseofulvin-loaded liposomes of various sizes, generated via different mechanical dispersion techniques [i.e., FTS (142 nm), MS (357 nm) and NS (813 nm)], but with essentially similar encapsulation efficiencies (about 93%). Results indicated that the extent of bioavailability of griseofulvin was improved 1.7-2.0 times when given in the form of liposomes (F1) compared to griseofulvin suspension. Besides that, there was an approximately two-fold enhancement of the extent of bioavailability following administration of griseofulvin-loaded liposomes with higher encapsulation efficiency (F2), compared to those of F1. Also, the results showed that the extent of bioavailability of liposomal formulations with smaller sizes were higher by approximately three times compared to liposomal formulation of a larger size. Nevertheless, a further size reduction of griseofulvin-loaded liposome (≤400 nm) did not promote the uptake or bioavailability of griseofulvin. In conclusion, high drug encapsulation efficiency and small liposome size could enhance the oral bioavailability of griseofulvin-loaded liposomes and therefore these two parameters deserve careful consideration during formulation.
    Matched MeSH terms: Biological Availability
  12. Fulltext Bioavailability of heavy metal in rice using in vitro digestion model
    Omar, N. A., Praveena, S. M., Hashim, Z., Aris, A. Z.
    International Food Research Journal, 2013;20(6):2979-2985.
    MyJurnal
    Rice is a carbohydrate, one of the plant-based foods that can accumulate heavy metal from soil and the irrigation water. Since total heavy metal always overestimates the amount of heavy metal available in rice, bioavailability of heavy metal is always preferred. Many studies have been done and found that in vitro methods offer an appealing alternative to human and animal studies. They can be simple, rapid, low in cost and may provide insights which not achievable in the in vivo studies. In vitro digestion model for rice may differ from other in vitro digestion models applied in soil or other type of foods studies. This review aims to provide an overview of in vitro digestion model used to determine bioavailability of heavy metal in rice, summarize health risk assessment application of heavy metal in rice studies and highlight the importance of health risk assessment to be included in the studies. Future exploration of in vitro digestion model and health risk assessment application on the bioavailability of heavy metal in rice was also suggested.
    Matched MeSH terms: Biological Availability
  13. Health Risk Assessment using in vitro digestion model in assessing bioavailability of heavy metal in rice: A preliminary study
    Omar NA, Praveena SM, Aris AZ, Hashim Z
    Food Chem, 2015 Dec 1;188:46-50.
    PMID: 26041162 DOI: 10.1016/j.foodchem.2015.04.087
    Little is known about the bioavailability of heavy metal contamination and its health risks after rice ingestion. This study aimed to determine bioavailability of heavy metal (As, Cd, Cu, Cr, Co, Al, Fe, Zn and Pb) concentrations in cooked rice and human Health Risk Assessment (HRA). The results found Zn was the highest (4.3±0.1 mg/kg), whereas As showed the lowest (0.015±0.001 mg/kg) bioavailability of heavy metal concentration in 22 varieties of cooked rice. For single heavy metal exposure, no potential of non carcinogenic health risks was found, while carcinogenic health risks were found only for As. Combined heavy metal exposures found that total Hazard Quotient (HQtotal) values for adult were higher than the acceptable range (HQTotal<1), whereas total Lifetime Cancer Risk (LCRTotal) values were higher than the acceptable range (LCRTotal values >1×10(-4)) for both adult and children. This study is done to understand that the inclusion of bioavailability heavy metal into HRA produces a more realistic estimation of human heavy metal exposure.
    Matched MeSH terms: Biological Availability*
  14. Fulltext Date palm and goat milk improve haematological parameters and availability of functional iron in iron deficient rats
    Nurainna Abd Majid, Zuriani Zainol, Nor Aripin Shamaan, Nazefah Abd Hamid, Nuruliza Roslan, Noor Fadzilah Zulkifli
    Malaysian Journal of Medicine and Health Sciences, 2020;16(3):52-59.
    MyJurnal
    Introduction: Iron deficiency anaemia (IDA) is endemic especially in the under-developed and developing countries and is a major public health concern. Improving nutrition is one of the ways to alleviate this condition. Consumption of locally available and affordable food such as date palm and goat milk which are rich in iron is one of the ways to overcome IDA. This study is aimed at evaluating the effect of date palm and goat milk supplementation on hae- matological parameters and iron bioavailability in IDA rats. Methods: 24 male Wistar rats were randomly divided into normal control and IDA group. The normal control was fed with normal diet and water ad libitum while the IDA group were fed on iron-deficient diet for two weeks to induce iron deficiency. The IDA rats were further divided into subgroups; each being supplemented with date palm, goat milk, a combination of date palm and goat milk, and ferrous fumarate as positive control. Blood were collected after 28 days for haematological parameters and iron profile determination. Iron bioavailability was assessed using the haemoglobin regeneration efficiency (HRE) index. Data was analysed by Student T Test and ANOVA using SPSS 23.0 software with p value < 0.05 considered as sta- tistically significant. Results: Supplementation of date palm and goat milk for 28 days significantly improved Hb, RBC, PCV, MCV, MCH, serum iron and transferrin saturation (p
    Matched MeSH terms: Biological Availability
  15. Fulltext In Vitro Evaluation of Curcumin-Encapsulated Chitosan Nanoparticles against Feline Infectious Peritonitis Virus and Pharmacokinetics Study in Cats
    Ng SW, Selvarajah GT, Hussein MZ, Yeap SK, Omar AR
    Biomed Res Int, 2020;2020:3012198.
    PMID: 32596292 DOI: 10.1155/2020/3012198
    Feline infectious peritonitis (FIP) is an important feline viral disease, causing an overridden inflammatory response that results in a high mortality rate, primarily in young cats. Curcumin is notable for its biological activities against various viral diseases; however, its poor bioavailability has hindered its potential in therapeutic application. In this study, curcumin was encapsulated in chitosan nanoparticles to improve its bioavailability. Curcumin-encapsulated chitosan (Cur-CS) nanoparticles were synthesised based on the ionic gelation technique and were spherical and cuboidal in shape, with an average particle size of 330 nm and +42 mV in zeta potential. The nanoparticles exerted lower toxicity in Crandell-Rees feline kidney (CrFK) cells and enhanced antiviral activities with a selective index (SI) value three times higher than that of curcumin. Feline-specific bead-based multiplex immunoassay and qPCR were used to examine their modulatory effects on proinflammatory cytokines, including tumour necrosis factor (TNF)α, interleukin- (IL-) 6, and IL-1β. There were significant decrements in IL-1β, IL-6, and TNFα expression in both curcumin and Cur-CS nanoparticles. Based on the multiplex immunoassay, curcumin and the Cur-CS nanoparticles could lower the immune-related proteins in FIP virus (FIPV) infection. The single- and multiple-dose pharmacokinetics profiles of curcumin and the Cur-CS nanoparticles were determined by high-performance liquid chromatography (HPLC). Oral delivery of the Cur-CS nanoparticles to cats showed enhanced bioavailability with a maximum plasma concentration (Cmax) value of 621.5 ng/mL. Incorporating chitosan nanoparticles to deliver curcumin improved the oral bioavailability and antiviral effects of curcumin against FIPV infection. This study provides evidence for the potential of Cur-CS nanoparticles as a supplementary treatment of FIP.
    Matched MeSH terms: Biological Availability
  16. Applications of Nanocarriers as Drug Delivery Vehicles for Active Phytoconstituents
    Ng PQ, Ling LSC, Chellian J, Madheswaran T, Panneerselvam J, Kunnath AP, et al.
    Curr Pharm Des, 2020;26(36):4580-4590.
    PMID: 32520681 DOI: 10.2174/1381612826666200610111013
    Many plant-based bioactive compounds have been serving as the origin of drugs since long ago and many of them have been proven to have medicinal value against various chronic diseases, including, cancer, arthritis, hepatic diseases, type-2 diabetes and cardiovascular diseases. However, their clinical applications have been limited due to their poor water solubility, stability, low bioavailability and extensive transformation due to the first-pass metabolism. The applications of nanocarriers have been proven to be able to improve the delivery of bioactive phytoconstituents, resulting in the enhancement of various pharmacokinetic properties and thereby increasing the therapeutic value of phytoconstituents. These biocompatible nanocarriers also exert low toxicity to healthy cells. This review focuses on the uses and applications of different types of nanocarriers to enhance the delivery of phytoconstituents for the treatment of various chronic diseases, along with comparisons related to bioavailability and therapeutic efficacy of nano phytoconstituents with native phytoconstituents.
    Matched MeSH terms: Biological Availability
  17. Domperidone nanocrystals with boosted oral bioavailability: fabrication, evaluation and molecular insight into the polymer-domperidone nanocrystal interaction
    Ndlovu ST, Ullah N, Khan S, Ramharack P, Soliman M, de Matas M, et al.
    Drug Deliv Transl Res, 2019 Feb;9(1):284-297.
    PMID: 30387048 DOI: 10.1007/s13346-018-00596-w
    The aim of this study was to employ experimental and molecular modelling approaches to use molecular level interactions to rationalise the selection of suitable polymers for use in the production of stable domperidone (DOMP) nanocrystals with enhanced bioavailability. A low-energy antisolvent precipitation method was used for the preparation and screening of polymers for stable nanocrystals of DOMP. Ethyl cellulose was found to be very efficient in producing stable DOMP nanocrystals with particle size of 130 ± 3 nm. Moreover, the combination of hydroxypropyl methylcellulose and polyvinyl alcohol was also shown to be better in producing DOMP nanocrystals with smaller particle size (200 ± 3.5 nm). DOMP nanosuspension stored at 2-8 °C and at room temperature (25 °C) exhibited better stability compared to the samples stored at 40 °C. Crystallinity of the unprocessed and processed DOMP was monitored by differential scanning calorimetry and powder X-ray diffraction. DOMP nanocrystals gave enhanced dissolution rate compared to the unprocessed drug substance. DOMP nanocrystals at a dose of 10 mg/kg in rats showed enhanced bioavailability compared to the raw drug substance and marketed formulation. A significant increase in plasma concentration of 2.6 μg/mL with a significant decrease in time (1 h) to reach maximum plasma concentration was observed for DOMP nanocrystals compared to the raw DOMP. Molecular modelling studies provided underpinning knowledge at the molecular level of the DOMP-polymer nanocrystal interactions and substantiated the experimental studies. This included an understanding of the impact of polymers on the size of nanocrystals and their associated stability characteristics.
    Matched MeSH terms: Biological Availability
  18. Pharmacokinetics of artemisinin-type compounds
    Navaratnam V, Mansor SM, Sit NW, Grace J, Li Q, Olliaro P
    Clin Pharmacokinet, 2000 Oct;39(4):255-70.
    PMID: 11069212
    Various compounds of the artemisinin family are currently used for the treatment of patients with malaria worldwide. They are characterised by a short half-life and feature the most rapidly acting antimalarial drugs to date. They are increasingly being used, often in combination with other drugs, although our knowledge of their main pharmacological features (including their absorption, distribution, metabolism and excretion) is still incomplete. Such data are particularly important in the case of combinations. Artemisinin derivatives are converted primarily, but to different extents, to the bioactive metabolite artenimol after either parenteral or gastrointestinal administration. The rate of conversion is lowest for artelinic acid (designed to protect the molecule against metabolism) and highest for the water-soluble artesunate. The absolute and relative bioavailability of these compounds has been established in animals, but not in humans, with the exception of artesunate. Oral bioavailability in animals ranges, approximately, between 19 and 35%. A first-pass effect is highly probably for all compounds when administered orally. Artemisinin compounds bind selectively to malaria-infected erythrocytes to yet unidentified targets. They also bind modestly to human plasma proteins, ranging from 43% for artenimol to 81.5% for artelinic acid. Their mode of action is still not completely understood, although different theories have been proposed. The lipid-soluble artemether and artemotil are released slowly when administered intramuscularly because of the 'depot' effect related to the oil formulation. Understanding the pharmacokinetic profile of these 2 drugs helps us to explain the characteristics of the toxicity and neurotoxicity. The water-soluble artesunate is rapidly converted to artenimol at rates that vary with the route of administration, but the processes need to be characterised further, including the relative contribution of pH and enzymes in tissues, blood and liver. This paper intends to summarise contemporary knowledge of the pharmacokinetics of this class of compounds and highlight areas that need further research.
    Matched MeSH terms: Biological Availability
  19. Fulltext Tolerability and pharmacokinetics of non-fixed and fixed combinations of artesunate and amodiaquine in Malaysian healthy normal volunteers
    Navaratnam V, Ramanathan S, Wahab MS, Siew Hua G, Mansor SM, Kiechel JR, et al.
    Eur J Clin Pharmacol, 2009 Aug;65(8):809-21.
    PMID: 19404632 DOI: 10.1007/s00228-009-0656-1
    There is limited pharmacokinetic data available for the combination artesunate + amodiaquine, which is used widely to treat uncomplicated malaria. This study examines the bioavailability and tolerability of a fixed (200 mg artesunate + 540 mg amodiaquine) and loose (200 mg + 612 mg) combination with a 2x2 cross-over design in 24 healthy volunteers.
    Matched MeSH terms: Biological Availability
  20. Fulltext Resveratrol-loaded PLGA nanoparticles mediated programmed cell death in prostate cancer cells
    Nassir AM, Shahzad N, Ibrahim IAA, Ahmad I, Md S, Ain MR
    Saudi Pharm J, 2018 Sep;26(6):876-885.
    PMID: 30202231 DOI: 10.1016/j.jsps.2018.03.009
    Resveratrol (RL), a natural polyphenol, is known for its diverse biological effects against various human cancer cell lines. But low aqueous solubility, poor bioavailability, and stability limit its efficacy against prostate cancer. In this study polymeric nanoparticles encapsulating resveratrol (RLPLGA) were designed and their cytotoxic and mode of apoptotic cells death against prostate cancer cell line (LNCaP) was determined. Nanoparticles were prepared by solvent displacement method and characterized for particle size, TEM, entrapment efficiency, DSC and drug release study. RLPLGA exhibited a significant decrease in cell viability with 50% and 90% inhibitory concentration (IC50 and IC90) of 15.6 ± 1.49 and 41.1 ± 2.19 μM respectively against the LNCaP cells. This effect was mediated by apoptosis as confirmed by cell cycle arrest at G1-S transition phase, externalization of phosphatidylserine, DNA nicking, loss of mitochondrial membrane potential and reactive oxygen species generation in LNCaP cells. Furthermore, significantly greater cytotoxicity to LNCaP cells was observed with nanoparticles as compared to that of free RL at all tested concentrations. RLPLGA nanoparticles presented no adverse cytotoxic effects on murine macrophages even at 200 μM. Our findings support the potential use of developed resveratrol loaded nanoparticle for the prostate cancer chemoprevention/ chemotherapy with no adverse effect on normal cells.
    Matched MeSH terms: Biological Availability
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