Displaying publications 1 - 20 of 37 in total

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  1. Fulltext Lipid effects on expulsion rate of amphotericin B from solid lipid nanoparticles
    Tan SW, Billa N
    AAPS PharmSciTech, 2014 Apr;15(2):287-95.
    PMID: 24318197 DOI: 10.1208/s12249-013-0056-9
    We aimed to investigate the effects that natural lipids, theobroma oil (TO) and beeswax (BW), might have on the physical properties of formulated nanoparticles and also the degree of expulsion of encapsulated amphotericin B (AmB) from the nanoparticles during storage. Lecithin and sodium cholate were used as emulsifiers whilst oleic acid (OA) was used to study the influence of the state of orderliness/disorderliness within the matrices of the nanoparticles on the degree of AmB expulsion during storage. BW was found to effect larger z-average diameter compared with TO. Lecithin was found to augment the stability of the nanoparticles imparted by BW and TO during storage. An encapsulation efficiency (%EE) of 59% was recorded when TO was the sole lipid as against 42% from BW. In combination however, the %EE dropped to 39%. When used as sole lipid, TO or BW formed nanoparticles with comparatively higher enthalpies, 21.1 and 23.3 J/g respectively, which subsequently caused significantly higher degree of AmB expulsion, 81 and 83% respectively, whilst only 11.8% was expelled from a binary TO/BW mixture. A tertiary TO/BW/OA mixture registered the lowest enthalpy at 8.07 J/g and expelled 12.6% of AmB but encapsulated only 22% of AmB. In conclusion, nanoparticles made from equal concentrations of TO and BW produced the most desirable properties and worthy of further investigations.
  2. Formulation variables affecting drug release from xanthan gum matrices at laboratory scale and pilot scale
    Billa N, Yuen KH
    AAPS PharmSciTech, 2000;1(4):E30.
    PMID: 14727895
    The purpose of this research was to study processing variables at the laboratory and pilot scales that can affect hydration rates of xanthan gum matrices containing diclofenac sodium and the rate of drug release. Tablets from the laboratory scale and pilot scale proceedings were made by wet granulation. Swelling indices of xanthan gum formulations prepared with different amounts of water were measured in water under a magnifying lens. Granules were thermally treated in an oven at 60 degrees C, 70 degrees C, and 80 degrees C to study the effects of elevated temperatures on drug release from xanthan gum matrices. Granules from the pilot scale formulations were bulkier compared to their laboratory scale counterparts, resulting in more porous, softer tablets. Drug release was linear from xanthan gum matrices prepared at the laboratory scale and pilot scales; however, release was faster from the pilot scales. Thermal treatment of the granules did not affect the swelling index and rate of drug release from tablets in both the pilot and laboratory scale proceedings. On the other hand, the release from both proceedings was affected by the amount of water used for granulation and the speed of the impeller during granulation. The data suggest that processing variables that affect the degree of wetness during granulation, such as increase in impeller speed and increase in amount of water used for granulation, also may affect the swelling index of xanthan gum matrices and therefore the rate of drug release.
  3. Fulltext Soliciting the Oral Route as a Logical Approach to Managing Colon Cancer
    Sabra R, Billa N
    Front Bioeng Biotechnol, 2021;9:645923.
    PMID: 33718345 DOI: 10.3389/fbioe.2021.645923
  4. Fulltext Improved Bioavailability of Poorly Soluble Drugs through Gastrointestinal Muco-Adhesion of Lipid Nanoparticles
    Tan SLJ, Billa N
    Pharmaceutics, 2021 Oct 31;13(11).
    PMID: 34834232 DOI: 10.3390/pharmaceutics13111817
    Gastrointestinal absorption remains indispensable in the systemic delivery of most drugs, even though it presents several challenges that, paradoxically, may also provide opportunities that can be exploited to achieve maximal bioavailability. Drug delivery systems made from nanoparticle carriers and especially, lipid carriers, have the potential to traverse gastrointestinal barriers and deploy in the lymphatic pathway, which aptly, is free from first pass via the liver. Several poorly soluble drugs have presented improved systemic bioavailability when couriered in lipid nanoparticle carriers. In this review, we propose an additional frontier to enhancing the bioavailability of poorly soluble drugs when encapsulated in lipid nano-carriers by imparting muco-adhesion to the particles through application of appropriate polymeric coating to the lipid carrier. The combined effect of gastrointestinal muco-adhesion followed by lymphatic absorption is a promising approach to improving systemic bioavailability of poorly soluble drugs following oral administration. Evidence to the potential of this approach is backed-up by recent studies within the review.
  5. Pharmacokinetics and tissue distribution of an orally administered mucoadhesive chitosan-coated amphotericin B-Loaded nanostructured lipid carrier (NLC) in rats
    Tan JSL, Roberts C, Billa N
    J Biomater Sci Polym Ed, 2020 02;31(2):141-154.
    PMID: 31612804 DOI: 10.1080/09205063.2019.1680926
    Oral delivery of amphotericin B (AmpB) is desirable because it provides a more patient-friendly mode of administration compared to the current delivery approach akin with the marketed AmpB formulations. The goal of the study was to investigate the pharmacokinetics and tissue distribution of orally administered chitosan-coated AmpB-loaded nanostructured lipid carriers (ChiAmpB NLC) administered to Sprague Dawley rats at a dose of 15 mg/kg. Orally administered ChiAmpB NLC resulted in a two-fold increase in the area under the curve (AUC0-∞) compared to the uncoated AmpB NLC and marketed Amphotret®. This enhanced bioavailability of AmpB suggests prolonged transit and retention of ChiAmpB NLC within the small intestine through mucoadhesion and subsequent absorption by the lymphatic pathway. The results show that mean absorption and residence times (MAT & MRT) were significantly higher from ChiAmpB NLC compared to the other two formulations, attesting to the mucoadhesive effect. The ChiAmpB NLC presented a lower nephrotic accumulation with preferential deposition in liver and spleen. Thus, the limitations of current marketed IV formulations of AmpB are potentially addressed with the ChiAmpB NLC in addition to utilizing this approach for targeting internal organs in visceral leishmaniasis.
  6. 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.
  7. Cetuximab-conjugated chitosan-pectinate (modified) composite nanoparticles for targeting colon cancer
    Sabra R, Billa N, Roberts CJ
    Int J Pharm, 2019 Dec 15;572:118775.
    PMID: 31678385 DOI: 10.1016/j.ijpharm.2019.118775
    In the present study, we successfully developed a cetuximab-conjugated modified citrus pectin-chitosan nanoparticles for targeted delivery of curcumin (Cet-MCPCNPs) for the treatment of colorectal cancer. In vitro analyses revealed that nanoparticles were spherical with size of 249.33 ± 5.15 nm, a decent encapsulation efficiency (68.43 ± 2.4%) and a 'smart' drug release profile. 61.37 ± 0.70% of cetuximab was adsorbed to the surface of the nanoparticles. Cellular uptake studies displayed enhanced internalization of Cet-MCPCNPs in Caco-2 (EGFR +ve) cells, which ultimately resulted in a significant reduction in cancer cell propagation. The cell cycle analysis indicated that Cet- MCPCNPs induced cell death in enhanced percentage of Caco-2 cells by undergoing cell cycle arrest in the G2/M phase. These data suggest that Cet-MCPCNPs represent a new and promising targeting approach for the treatment of colorectal cancer.
  8. Correlating gastric emptying of amphotericin B and paracetamol solid lipid nanoparticles with changes in particle surface chemistry
    Amekyeh H, Billa N, Roberts C
    Int J Pharm, 2017 Jan 30;517(1-2):42-49.
    PMID: 27923696 DOI: 10.1016/j.ijpharm.2016.12.001
    Oral delivery of pharmaceuticals requires that they retain their physical and chemical attributes during transit within the gastrointestinal (GI) tract, for the manifestation of desired therapeutic profiles. Solid lipid nanoparticles (SLNs) are used as carriers to improve the absorption of hydrophobic drugs. In this study, we examine the stability of amphotericin B (AmB) and paracetamol (PAR) SLNs in simulated GI fluids during gastric emptying. On contact with the simulated fluids, the particles increased in size due to ingress of the dissolution media into the particles. Simulated gastric emptying revealed that the formulations had mean sizes <350nm and neutral surface charges, both of which are optimal for intestinal absorption of SLNs. There was ingress of the fluids into the SLNs, followed by diffusion of the dissolved drug, whose rate depended on the solubility of the loaded-drug in the particular medium. Time-of-flight secondary ion mass spectrometry analyses indicated that drug loading followed the core-shell model and that the AmB SLNs have a more drug-enriched core than the PAR SLNs do. The AmB SLNs are therefore a very suitable carrier of AmB for oral delivery. The stability of the SLNs in the simulated GI media indicates their suitability for oral delivery.
  9. Gamma-scintigraphic study of the gastrointestinal transit and in vivo dissolution of a controlled release diclofenac sodium formulation in xanthan gum matrices
    Billa N, Yuen KH, Khader MA, Omar A
    Int J Pharm, 2000 May 15;201(1):109-20.
    PMID: 10867269
    A xanthan gum matrix controlled release tablet formulation containing diclofenac sodium was evaluated in vitro and was found to release the drug at a uniform rate. The gastrointestinal transit behaviour of the formulation as determined by gamma scintigraphy, using healthy male volunteers under fasted and fed conditions, indicated that gastric emptying was delayed with food intake. In contrast, the small intestinal transit remained practically unchanged under both food statuses. Therefore, the delay in caecal arrival observed in the fed state can be attributed to the delay in gastric emptying. Rate of diclofenac sodium absorption was generally higher in the fed state compared to the fasted state, however the total amount absorbed under both food statuses remained practically the same. The rate of in vivo dissolution of the drug in the fed state was faster compared to that in the fasted state. Thus, at the time of caecal arrival, in vivo dissolution was complete in the fed state, unlike in the fasted state, where almost 60% of the drug was delivered to the colon.
  10. Mucoadhesive Chitosan-Pectinate Nanoparticles for the Delivery of Curcumin to the Colon
    Alkhader E, Billa N, Roberts CJ
    AAPS PharmSciTech, 2017 May;18(4):1009-1018.
    PMID: 27582072 DOI: 10.1208/s12249-016-0623-y
    In the present study, we report the properties of a mucoadhesive chitosan-pectinate nanoparticulate formulation able to retain its integrity in the milieu of the upper gastrointestinal tract and subsequently, mucoadhere and release curcumin in colon conditions. Using this system, we aimed to deliver curcumin to the colon for the possible management of colorectal cancer. The delivery system comprised of a chitosan-pectinate composite nanopolymeric with a z-average of 206.0 nm (±6.6 nm) and zeta potential of +32.8 mV (±0.5 mV) and encapsulation efficiency of 64%. The nanoparticles mucoadhesiveness was higher at alkaline pH compared to acidic pH. Furthermore, more than 80% release of curcumin was achieved in pectinase-enriched medium (pH 6.4) as opposed to negligible release in acidic and enzyme-restricted media at pH 6.8. SEM images of the nanoparticles after exposure to the various media indicate a retained matrix in acid media as opposed to a distorted/fragmented matrix in pectinase-enriched medium. The data strongly indicates that the system has the potential to be applied as a colon-targeted mucoadhesive curcumin delivery system for the possible treatment of colon cancer.
  11. Multiboronic acid-conjugated chitosan scaffolds with glucose selectivity to insulin release
    Siddiqui NA, Billa N, Roberts CJ
    J Biomater Sci Polym Ed, 2017 Jun;28(8):781-793.
    PMID: 28278045 DOI: 10.1080/09205063.2017.1301774
    The principal challenge for the use of boronic acids (BA) as glucose sensors is their lack of specificity for glucose. We examined the selectivity of and insulin release from two boronic acids- (2-formyl-3-thienylboronic acid (FTBA) and 4-formylphenylboronic acid (FPBA)) conjugated chitosan scaffolds to glucose and fructose. Adsorption of glucose to BA: chitosan conjugates was dose-dependent up to 1:1 at 35 and 42% for FPBA and FTBA respectively but the FTBA conjugates adsorbed more glucose and fructose at respective FPBA ratios. The affinity of both BA conjugates to glucose decreased with increase in BA ratio. On the other hand, the affinity of both BA conjugates for fructose decreased from ratio 1:1 to 2:1 then rose again at 3:1. Insulin release from FPBA nanoparticles (FPBAINP) and FTBA nanoparticles (FTBAINP) were both concentration-dependent within glyceamically relevant values (1-3 mg/ml glucose and 0.002 mg/ml fructose). Furthermore, the total amounts of insulin released from FPBAINP in both the media were higher than from FTBAINP. Both FPBAINP and FTBAINP have the potential for development as a glucose-selective insulin delivery system in physiological settings.
  12. Mucoadhesive chitosan-coated nanostructured lipid carriers for oral delivery of amphotericin B
    Ling Tan JS, Roberts CJ, Billa N
    Pharm Dev Technol, 2019 Apr;24(4):504-512.
    PMID: 30132723 DOI: 10.1080/10837450.2018.1515225
    This study describes the properties of an amphotericin B-containing mucoadhesive nanostructured lipid carrier (NLC), with the intent to maximize uptake within the gastrointestinal tract. We have reported previously that lipid nanoparticles can significantly improve the oral bioavailability of amphotericin B (AmpB). On the other hand, the aggregation state of AmpB within the NLC has been ascribed to some of the side effects resulting from IV administration. In the undissolved state, AmpB (UAmpB) exhibited the safer monomeric conformation in contrast to AmpB in the dissolved state (DAmpB), which was aggregated. Chitosan-coated NLC (ChiAmpB NLC) presented a slightly slower AmpB release profile as compared to the uncoated formulation, achieving 26.1% release in 5 hours. Furthermore, the ChiAmpB NLC formulation appeared to prevent the expulsion of AmpB upon exposure to simulated gastrointestinal pH media, whereby up to 63.9% of AmpB was retained in the NLC compared to 56.1% in the uncoated formulation. The ChiAmpB NLC demonstrated mucoadhesive properties in pH 5.8 and 6.8. Thus, the ChiAmpB NLC formulation is well-primed for pharmacokinetic studies to investigate whether delayed gastrointestinal transit may be exploited to improve the systemic bioavailability of AmpB, whilst simultaneously addressing the side-effect concerns of AmpB.
  13. Antifungal and Mucoadhesive Properties of an Orally Administered Chitosan-Coated Amphotericin B Nanostructured Lipid Carrier (NLC)
    Ling JTS, Roberts CJ, Billa N
    AAPS PharmSciTech, 2019 Mar 05;20(3):136.
    PMID: 30838459 DOI: 10.1208/s12249-019-1346-7
    Surface-modified nanostructured lipid carriers (NLC) represent a promising mode of drug delivery used to enhance retention of drugs at absorption site. Formulated chitosan-coated amphotericin-B-loaded NLC (ChiAmp NLC) had a size of 394.4 ± 6.4 nm, encapsulation and loading efficiencies of 86.0 ± 3% and 11.0 ± 0.1% respectively. Amphotericin-B release from NLCs was biphasic with no changes in physical properties upon exposure to simulated gastrointestinal conditions. Antifungal properties of Amphotericin-B and ChiAmpB NLC were comparable but ChiAmpB NLC was twice less toxic to red blood cells and ten times safer on HT-29 cell lines. In vitro mucoadhesion data were observed ex vivo, where ChiAmpB NLC resulted in higher retention within the small intestine compared to the uncoated formulation. The data strongly offers the possibility of orally administering a non-toxic, yet effective Amphotericin-B nanoformulation for the treatment of systemic fungal infections.
  14. Diclofenac release from eudragit-containing matrices and effects of thermal treatment
    Billa N, Yuen KH, Peh KK
    Drug Dev Ind Pharm, 1998 Jan;24(1):45-50.
    PMID: 15605596
    Ethyl acrylate-methyl methacrylate copolymer (Eudragit NE40D) was evaluated as matrix material for preparing controlled-release tablets of diclofenac sodium. Drug release could be modified in a predictable manner by varying the Eudragit NE40D content, but was pH dependent, being markedly reduced at lower pH. This could be attributed to the low solubility of the drug at these pH values. Thermal treatment of the tablets at 60 degrees C was also found to affect the rate of drug release, which was found to decrease with an increase in the treatment duration, but could be stabilized after 96 hr of treatment. This was also associated with a corresponding increase in the tablet tensile strength. However, treatment of the granules for 5 hr prior to compaction into tablets could shorten the stabilizing time of the drug release to 48 hr and that of the tensile strength to 24 hr. The effect of thermal treatment may be ascribed to better coalescence of the Eudragit particles to form a fine network, resulting in matrix of higher tortuosity and lower porosity.
  15. Comparative bioavailability study of a generic naltrexone tablet preparation
    Yuen KH, Peh KK, Billa N
    Drug Dev Ind Pharm, 1999 Mar;25(3):353-6.
    PMID: 10071829
    The bioavailability of a generic preparation of naltrexone (Narpan) was compared with the innovator product, Trexan. Twelve healthy volunteers participated in the study, conducted according to a completely randomized, two-way crossover design. The preparations were compared using the parameters 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 observed between the logarithmic transformed AUC0-infinity and the logarithmically transformed Cmax values of the two preparations. Also, no statistically significant difference was observed between the untransformed Tmax values. In addition, the 90% confidence interval for the ratio of the logarithmic transformed AUC0-infinity values of Narpan over those of Trexan was found to lie between 0.87 and 1.01, while that of the logarithmic transformed Cmax values was between 0.94 and 1.23, both being within the bioequivalence limit of 0.80-1.25. The numerical values of the elimination half-life (t1/2) obtained with the two preparations were also not significantly different and were comparable to those reported in the literature.
  16. Fulltext A gastrointestinal transit study on amphotericin B-loaded solid lipid nanoparticles in rats
    Amekyeh H, Billa N, Yuen KH, Chin SL
    AAPS PharmSciTech, 2015 Aug;16(4):871-7.
    PMID: 25588365 DOI: 10.1208/s12249-014-0279-4
    The gastrointestinal (GI) transit behavior of and absorption from an amphotericin B (AmB) solid lipid nanoformulation (SLN) in rats was investigated. We aimed to estimate the gastric emptying time (GET) and cecal arrival time (CAT) of AmB SLN in rats as animal models. From these two parameters, an insight on the absorption window of AmB was ascertained. Three types of SLNs, AmB, paracetamol (PAR), and sulfasalazine (SSZ), were similarly formulated using beeswax/theobroma oil composite as the lipid matrix and characterized with regard to size, viscosity, density, migration propensity within agarose gel, in vitro drug release, morphology, gastrointestinal transit, and in vivo absorption. The GET and CAT were estimated indirectly using marker drugs: PAR and sulfapyridine (SP). All three types of SLNs exhibited identical properties with regard to z-average, viscosity, relative density, and propensity to migrate. PAR was absorbed rapidly from the small intestine following emptying of the SLNs giving the T50E (time for 50% absorption of PAR) to be 1.6 h. SP was absorbed after release and microbial degradation of SSZ from SLN in the colon with a lag time of 2 h post-administration, serving as the estimated cecal arrival time of the SLNs. AmB within SLN was favorably absorbed from the small intestine, albeit slowly.
  17. Cellular uptake and anticancer effects of mucoadhesive curcumin-containing chitosan nanoparticles
    Chuah LH, Roberts CJ, Billa N, Abdullah S, Rosli R
    Colloids Surf B Biointerfaces, 2014 Apr 1;116:228-36.
    PMID: 24486834 DOI: 10.1016/j.colsurfb.2014.01.007
    Curcumin, which is derived from turmeric has gained much attention in recent years for its anticancer activities against various cancers. However, due to its poor absorption, rapid metabolism and elimination, curcumin has a very low oral bioavailability. Therefore, we have formulated mucoadhesive nanoparticles to deliver curcumin to the colon, such that prolonged contact between the nanoparticles and the colon leads to a sustained level of curcumin in the colon, improving the anticancer effect of curcumin on colorectal cancer. The current work entails the ex vivo mucoadhesion study of the formulated nanoparticles and the in vitro effect of mucoadhesive interaction between the nanoparticles and colorectal cancer cells. The ex vivo study showed that curcumin-containing chitosan nanoparticles (CUR-CS-NP) have improved mucoadhesion compared to unloaded chitosan nanoparticles (CS-NP), suggesting that curcumin partly contributes to the mucoadhesion process. This may lead to an enhanced anticancer effect of curcumin when formulated in CUR-CS-NP. Our results show that CUR-CS-NP are taken up to a greater extent by colorectal cancer cells, compared to free curcumin. The prolonged contact offered by the mucoadhesion of CUR-CS-NP onto the cells resulted in a greater reduction in percentage cell viability as well as a lower IC50, indicating a potential improved treatment outcome. The formulation and free curcumin appeared to induce cell apoptosis in colorectal cancer cells, by arresting the cell cycle at G2/M phase. The superior anticancer effects exerted by CUR-CS-NP indicated that this could be a potential treatment for colorectal cancer.
  18. Formation and characterization of pDNA-loaded alginate microspheres for oral administration in mice
    Nograles N, Abdullah S, Shamsudin MN, Billa N, Rosli R
    J Biosci Bioeng, 2012 Feb;113(2):133-40.
    PMID: 22093752 DOI: 10.1016/j.jbiosc.2011.10.003
    Alginate, a natural polysaccharide, was explored in this study as an oral delivery vehicle of a mammalian expression vector into the murine intestinal mucosa. Alginate microspheres were produced through water-in-oil (W/O) emulsification method. Average diameter sizes of microspheres were 46.88 μm±3.07 μm with significant size reduction upon utilization of 1.0% Span80. Plasmid DNA (pDNA) carrying green fluorescent protein reporter gene (GFP), pVAX-GFP, was encapsulated within microspheres at efficiencies of 72.9 to 74.4%, carrying maximum load of 6 μg pDNA. Alginate microspheres demonstrated shrinkage in pH 1.2 and swelling in pH 9.0 with pDNA release about twice the amount released in acidic environment. Oral delivery of pVAX-GFP loaded-microspheres, at 50 μg, 100 μg and 150 μg dose, was performed on BALB/c mice. Tissue biodistribution, investigated through flow cytometric analysis, demonstrated GFP positive intestinal cells (<1.0%) with 1.3-fold higher levels for the 100 μg dose; therefore suggesting feasibility of the approach for oral gene delivery and vaccination.
  19. Effect of Food Status on the Gastrointestinal Transit of Amphotericin B-Containing Solid Lipid Nanoparticles in Rats
    Amekyeh H, Billa N, Yuen KH, Lim SC
    AAPS PharmSciTech, 2015 Oct 28.
    PMID: 26511938
    Amphotericin B (AmB) is poorly absorbed from the gastrointestinal tract. Recent studies have suggested enhanced drug absorption from solid lipid nanoparticles (SLN). Little is known of the fate of AmB absorption within the gastrointestinal tract, and no gastrointestinal transit study has yet been performed on AmB-containing nano-formulations. We aimed to investigate the effect of food on the gastrointestinal transit properties of an AmB-containing SLN in rats. Three SLNs containing AmB, paracetamol, or sulfasalazine were formulated using cocoa butter and beeswax as lipid matrices and simultaneously administered orally to Sprague-Dawley rats. Paracetamol and sulfapyridine were used as marker drugs for estimating gastric emptying and cecal arrival, respectively. The pharmacokinetic data generated for paracetamol and sulfapyridine were used in estimating the absorption of the AmB SLNs in the small and large intestines, respectively. A delayed rate of AmB absorption was observed in the fed state; however, the extent of absorption was not affected by food. Specifically, the percentages of AmB absorption during the fasted state in the stomach, small intestine, and colon were not significantly different from absorption within the respective regions in the fed state. In both states, however, absorption was highest in the colon and appeared to be a combination of absorption from the small intestine plus absorption proper within the colon. The study suggests that AmB SLN, irrespective of food status, is slowly but predominantly taken up by the lymph, making the small intestine the most favorable site for the delivery of the AmB SLNs.
  20. Estimated coefficient of variation values for sample size planning in bioequivalence studies
    Yuen KH, Wong JW, Yap SP, Billa N
    Int J Clin Pharmacol Ther, 2001 Jan;39(1):37-40.
    PMID: 11204936
    OBJECTIVE: The aim of the present communication is to provide information regarding the intrasubject coefficent of variation obtained from 30 bioequivalence studies covering 16 drugs which can be used for estimation of sample size. Additionally, an attempt was also made to estimate the test power of each of the studies conducted.

    METHODS: The intrasubject coefficient of variation was estimated from the residual mean square error obtained from analysis of variance of the parameters AUC0-infinity, Cmax and Cmax/AUC0-infinity after logarithmic transformation. The test power in the analyses of the above parameters was subsequently estimated using nomograms provided by Diletti et al. [1991].

    RESULTS AND CONCLUSION: Thirty products covering 16 drugs were studied in which 22 were immediate-release (including one dispersible tablet) and 8 were sustained-release formulations. The intrasubject coefficient of variation for the parameter AUC0-infinity was smaller than Cmax, and hence considerably more studies were able to attain a power of greater than 80% using 12 volunteers for the AUC0-infinity, compared to the Cmax. However, the variability in the Cmax could be reduced by using the parameter Cmax/ AUC0-infinity, and thus, provide a more realistic estimation of sample size, since the latter reflects only the rate of absorption and not both the rate and extent as in the case of Cmax [Endrenyi et al. 1991].

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