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The excipient usefulness of carbosil and Landolphia owariensis in two oil-based self-emulsifying formulations
Obitte Nicholas,Chukwu Amarauche
Asian Journal of Pharmaceutics , 2010,
Abstract: The objective of this work was to improve on the solubility of ibuprofen using two vegetable oil-based self-emulsifying formulations (SEFs) and to evaluate the potential usefulness of Carbosil (CARB) and Landolphia owariensis latex (LOL) in them. Isotropicity, drug solubility, viscosity, emulsification time (EMT), drug release, aqueous dilution, postemulsification drug precipitation and refrigeration tests were carried out on the coconut oil (CO) and shea butter oil (SBO)-based SEFs. Results showed that only four out of nine batches of the SEFs passed the preformulation isotropicity test. A 100-mg quantity proved to be the maximum amount of drug that could be dissolved by the SEFs to form a stable solution. After 72 hrs all the SEFs still retained stability. All of CO SEFs witnessed remarkable phase separation or drug precipitation However, SBO SEFs having oil:surfactant:cosurfactant ratio of 35:45:20 and containing LOL or LOL-CARB blend lost isotropicity or displayed drug precipitation 6 months later. Refrigeration temperature did not introduce any form of instability or phase separation. Similar viscosities were recorded by the two oil-based SEFs. However, little but inconsistent variation in viscosity was observed between SBO SEFS and LOL-containing SEFs. Aqueous dilution and postemulsification drug precipitation test indicated absence of phase separation and drug precipitation, respectively. Drug-release studies showed that the t 50 of SBO SEFs almost ranked equally with SBO SEFs containing LOL. CO SEFs emulsified at a longer time than those of SBO. SEFs distinctly recorded higher EMTs than those with LOL or CARB-LOL blend. In conclusion, solubility of ibuprofen was improved, CARB gelled the SEFs while LOL reduced their EMTs.
Development and Evaluation of Novel Self-Nanoemulsifying Drug Delivery Systems Based on a Homolipid from Capra hircus and Its Admixtures with Melon Oil for the Delivery of Indomethacin
Nicholas C. Obitte,Kenneth C. Ofokansi,Franklin C. Kenechukwu
Journal of Pharmaceutics , 2014, DOI: 10.1155/2014/340486
Abstract: In this study, goat fat (Capra hircus) and melon oil were extracted and used to formulate self-nanoemulsifying drug delivery systems (SNEDDS) based on either goat fat alone or its admixture with melon oil by employing escalating ratios of oil(s), surfactant blend (1?:?1 Tween 60 and Tween 80), and cosurfactant (Span 85), with or without carbosil, a glidant, for the delivery of indomethacin. The formulations were encapsulated in hard gelatin capsules and then assessed using isotropicity test, aqueous dilution stability and precipitation propensity, absolute drug content, emulsification time, in vitro drug release, and anti-inflammatory activity. The SNEDDS exhibited low precipitation propensity and excellent stability on copious dilution, as well as high drug release in vitro and in vivo. The inhibition produced by the SNEDDS was comparable to that of indomethacin injection (positive control) for much of the 5?h test period, indicating a high degree of bioavailability of the administered SNEDDS. The absolute drug contents and emulsification times fell within narrow limits. This study has shown that a 1?:?1 ratio of melon oil and goat fat could confer favourable properties with respect to drug release and anti-inflammatory activity on SNEDDS for the delivery of indomethacin, thus encouraging further development of the formulations. 1. Introduction The nonsteroidal anti-inflammatory drugs (NSAIDs) have remained the mainstay of the treatment and management of inflammatory disorders. Despite enormous innovations in novel drug delivery systems (NDDS) through alternative routes, oral drug delivery of NSAIDs has been the most common and preferred route of drug administration [1]. Its status is primarily a consequence of the wide acceptability of this “natural” route, better safety vis-à-vis the parenteral route, low cost of therapy, and improved patient compliance. With an increasing number of lipophilic drugs under development, homolipids and heterolipids have gained renewed interests as excipients for myriads of drug delivery systems [2]. Lipid-based formulations have been shown to enhance the bioavailability of orally administered drugs [3–6]. The oral delivery of lipophilic drugs presents a major challenge because of the low aqueous solubility. The Biopharmaceutics classification system (BCS) [7] classifies drugs into four categories depending on their solubility and permeability characteristics. According to this scheme, indomethacin belongs to class II drugs whose solubility is too low to be consistent with complete absorption. For this class of
The Physicochemical Evaluation and Applicability of Landolphia owariensis latex as a Release Modulating Agent in its Admixture with Carbosil in Ibuprofen-loaded Self-Emulsifying Oil Formulations
N C Obitte,A Chukwu,V I Onyishi,BC N Obitte
International Journal of Applied Research in Natural Products , 2009,
Abstract: Summary: The need to address the problematic gastric irritation side effects and inconsistent bioavailability of most poorly soluble drugs has drawn the attention of researchers to self emulsifying drug delivery system as one of the possible solutions to these problems. Secondly self emulsifying oil formulations good as they may be could be associated with leakage from their hard gelatin capsules. This further motivated the introduction of gelling agents to address this problem. The objective of this work was to investigate some preliminary properties of Landolphia owariensis latex, including its applicability as a release modulating agent when admixed with Carbosil , a gelling agent in Ibuprofen-loaded Palm Kernel oil (PKO)-based self-emulsifying oil formulations (SEOFs). Purification and precipitation were carried out on the oil and the latex respectively. Some physicochemical properties of the latex were also determined. SEOFs were formulated using varying concentrations of PKO, Tween 80 and Span 85 and thereafter tested for isotropicity. Drug-loaded SEOFs with or without Landolphia owariensis latex (LOL) and Carbosil-LOL admixture respectively were evaluated for stability, emulsification time, drug release, aqueous dilution, freeze thaw and drug precipitation tests. Results showed that LOL contained some phytocostituents, had a reasonable adhesive strength, and could retard aqueous permeation. Three out of nine batches of the SEOFs passed the isotropicity test, witnessed no phase separation when emulsified and diluted, and could resist drug precipitation after dilution. LOL did not at all delay drug release from SEOFs unlike LOL-Carbosil admixture. LOL-Carbosil admixture significantly (p<0.05) reduced emulsification time. There was no consistent trend in the dynamic viscosity result. Stability of the SEOFs was maintained at refrigeration temperature of 20C. The above results indicated that LOL, an oil-soluble latex possesses excipient usefulness when incorporated into SEOFs and can therefore be used to modulate the drug retarding effect of Carbosil in their SEOF formulations while retaining Carbosil’s gelling property. Industrial relevance: The major challenge confronting the biopharmaceutical properties of some nonsteroidal anti-inflammatory drugs and poorly water soluble drugs include gastric irritation and poor GIT solubility/unpredictable bioavailability respectively. Self-emulsifying oil formulation is a lipid-based drug delivery system that addresses the above two challenges by fine globule-drug entrapment/solubilisation. In the GIT the o/w
Self-Nanoemulsifying Drug Delivery Systems Based on Melon Oil and its Admixture with a Homolipid from Bos indicus for the Delivery of Indomethacin
NC Obitte, KC Ofokansi, IT Nzekwe, CO Esimone, IE Okoye
Tropical Journal of Pharmaceutical Research , 2011,
Abstract: Purpose: To formulate self-nanoemulsifying drug delivery systems (SNEDDS) based on melon oil and its admixture with a homolipid from Bos indicus (cow fat) for the delivery of indomethacin, a hydrophobic anti-inflammatory agent. Method: Melon oil and cow fat were extracted by standard methods and used in the formulation of SNEDDS based on either melon oil alone, or its admixture with cow fat by utilizing varying ratios of oil(s), surfactants and co-surfactants, with or without carbosil, a glidant. The formulations were encapsulated in hard gelatin capsules and then evaluated using relevant parameters including isotropicity tests, dilution stability, precipitation propensity, emulsification time, absolute drug content, in vitro drug release, and anti-inflammatory activity in an animal model. Results: Stable and negatively charged colloidal dispersions (zeta potential: -10.4 to -13.4 mV) in the nano size range (195 - 210 nm) were formed. Formulation of indomethacin as SNEDDS not only preserved the activity of the drug, but also guaranteed anti-inflammatory activity comparable to that of indomethacin injection. The inhibition produced by the drug-loaded SNEDDS and the positive control were identical for much of the 5 h test period, indicating a high degree of bioavailability of the administered SNEDDS formulation. Conclusion: A 1:1 ratio of melon oil and cow fat could be used in the formulation and delivery of indomethacin-loaded SNEDDS with satisfactory properties and acceptable product performance. The anti-inflammatory activity of indomethacin was preserved in the formulation.
The use of a pH-dependent and Non pH-dependent Natural Hydrophobic Biopolymer (Landolphia owariensis latex) as Capsule Coating Agents in in vitro Controlled Release of Metronidazole for Possible Colon Targeted Delivery
N C Obitte,A Chukwu,I V Onyishi
International Journal of Applied Research in Natural Products , 2010,
Abstract: Summary: Orally administered metronidazole often requires just a fraction of the administered dose for optimum local activity in the colon. Any formulation design that can target drug to the colon may require dose reduction while improving therapeutic activity. Colon targeted drug delivery achieves this fit. The objective of this work therefore was to evaluate the in vitro effect of, the percentage of surface area of capsule surface coated with Landolphia owariensis latex (LOL), particle size of granules, and %w/w of matrix former (methylcellulose) on the release of metronidazole from coated hard gelatine capsules for possible delivery to the colon. Metronidazole granules were prepared by the wet granulation technique and appropriately encapsulated prior to primary coating of capsule with Eudragit L-100 and secondary coating with LOL. Capsules having primary coating of Eudragit L-100 were coated with LOL atop 50% or 85% capsule surface. In vitro drug release was carried out sequentially in media of pH 1.2(0.1N HCl), 6.8 and 7.4(phosphate buffer solution) respectively. The dissolution data were subjected to kinetic treatment. Results showed that the greatest quantity of drug release took place at pH 7.4 over 9-20 h. Univariate analysis of variance indicated that surface area of capsule coated with LOL had a significant (p<0.05) effect on both amount of drug released and time of release at pH 7.4.Matrix former concentration also significantly (p<0.05) affected the quantity of drug released and time of release (T7.4) at pH 7.4. Most of the capsules prepared with 4% methylcellulose had better fit than those of 1% on the applied kinetic models. Capsules with 85% surface coated with LOL recorded higher dissolution efficiency (DE) and mean dissolution time (MDT) values, except in a few cases. Landolphia owariensis latex, has therefore proved to be a potentially useful polymer for possible achievement of colon targeted drug delivery. Industrial relevance: Landolphia owariensis latex is an ignored part of the climber tree. It can be cultivated and tapped to commercial scale as in rubber. There is presently a patent based on colon targeted technology which adopted capsule coating approach. The dip method of coating employed in this article is a common technology in capsule manufacture; therefore coating of the capsules with our natural biopolymer and Eudragit L-100 is not going to be tasking. This double hydrophobic coating technique prolongs drug release enough to convey the capsule to the colon with greatest quantity of the drug intact. This makes colon drug
Preliminary Studies on Two Vegetable Oil Based Self Emulsifying Drug Delivery System (SEDDS) for the Delivery of Metronidazole, A Poorly Water Soluble Drug
N.C. Obitte,H. Ezeiruaku,V.I. Onyishi
Journal of Applied Sciences , 2008,
Abstract: A preliminary evaluation was carried out on metronidazole-loaded Self Emulsifying Drug Delivery System (SEDDS) using two vegetable oils-Palm Kernel Oil (PKO) and Palm Oil (PO). Purification of oils, drug solubility in the oils, pre/post formulation isotropicity tests, emulsification times and release studies of metronidazole from the SEDDS were carried out. Results indicated solubility values of 4.441 and 4.654%w/w, respectively for metronidazole in PKO and PO. Preformulation isotropicity test revealed that out of the 24 batches evaluated 10 of the SEDDS formulations containing different oil: surfactant ratios and PKO:PO admixtures were found to be isotropic after 5 h. However when the SEDDS were loaded with metronidazole there was a reduction in the number (to 7) of formulations that maintained isotropicity and stability after 72 h. All the batches had emulsification times of less than two minutes except batch 4D with oil:surfactant concentration of 50:50. The release profile showed that most of the formulations released 50% of drug in less than 8 min and 85% of drug in less than 30 min. We therefore conclude that SEDDS containing the two vegetable oils are potential alternatives when immediate release and delivery of metronidazole is the primary motivation.
Three Philosophical Problems about Consciousness and their Possible Resolution  [PDF]
Nicholas Maxwell
Open Journal of Philosophy (OJPP) , 2011, DOI: 10.4236/ojpp.2011.11001
Abstract: Three big philosophical problems about consciousness are: Why does it exist? How do we explain and understand it? How can we explain brain-consciousness correlations? If functionalism were true, all three problems would be solved. But it is false, and that means all three problems remain unsolved (in that there is no other obvious candidate for a solution). Here, it is argued that the first problem cannot have a solution; this is inherent in the nature of explanation. The second problem is solved by recognizing that (a) there is an explanation as to why science cannot explain consciousness, and (b) consciousness can be explained by a different kind of explanation, empathic or “personalistic” explanation, compatible with, but not reducible to, scientific explanation. The third problem is solved by exploiting David Chalmers“principle of structural coherence”, and involves postulating that sensations experienced by us–visual, auditory, tactile, and so on–amount to minute scattered regions in a vast, multi dimensional “space” of all possible sensations, which vary smoothly, and in a linear way, throughout the space. There is also the space of all possible sentient brain processes. There is just one, unique one-one mapping between these two spaces that preserves continuity and linearity. It is this which provides the explanation as to why brain processes and sensations are correlated as they are. I consider objections to this unique-matching theory, and consider how the theory might be empirically confirmed.
Origins and Mechanisms in the Development of Major Mental Disorders: A Clinical Approach  [PDF]
Nicholas Pediaditakis
Journal of Behavioral and Brain Science (JBBS) , 2012, DOI: 10.4236/jbbs.2012.22030
Abstract: This paper considers the following collective significance of the shared, clinical characteristics of the major mental disorders (MMDs), their co-morbidities, overlaps and pharmacological responses with the following conclusions: 1) These disorders have a common, initial, neurodevelopmental origin. 2) They can occur probabilistically on susceptible individuals, on account of pre-existing, extreme, temperamental variances-signifying underlying structural variance. 3) Each of these syndromes can be considered the expression of disturbances in the overall, common, operating mode of brain function which normally ensures the synchrony, coordination, elegance and subtlety in the expression of all the brain’s higher faculties. 4) Lastly, this function is a complex, emergent phenomenon based on the individual’s temperamental/structural underlying makeup, switching intermittently from a normal phase to a pathologically, ordered one-the latter phase expressing itself with symptoms made up of expressing either/or, antithetical substitutes for each of the MMDs-similar to the fluctuations found in patient’s with Parkinson’s disease.
Origins and Mechanisms in the Development of Major Mental Disorders: A Clinical Approach  [PDF]
Nicholas Pediaditakis
Journal of Behavioral and Brain Science (JBBS) , 2012, DOI: 10.4236/jbbs.2012.22030
Abstract: This paper considers the following collective significance of the shared, clinical characteristics of the major mental disorders (MMDs), their co-morbidities, overlaps and pharmacological responses with the following conclusions: 1) These disorders have a common, initial, neurodevelopmental origin. 2) They can occur probabilistically on susceptible individuals, on account of pre-existing, extreme, temperamental variances-signifying underlying structural variance. 3) Each of these syndromes can be considered the expression of disturbances in the overall, common, operating mode of brain function which normally ensures the synchrony, coordination, elegance and subtlety in the expression of all the brain’s higher faculties. 4) Lastly, this function is a complex, emergent phenomenon based on the individual’s temperamental/structural underlying makeup, switching intermittently from a normal phase to a pathologically, ordered one-the latter phase expressing itself with symptoms made up of expressing either/or, antithetical substitutes for each of the MMDs-similar to the fluctuations found in patient’s with Parkinson’s disease.
Three Criticisms of Newton’s Inductive Argument in the Principia  [PDF]
Nicholas Maxwell
Advances in Historical Studies (AHS) , 2014, DOI: 10.4236/ahs.2014.31002
Abstract: In this paper, I discuss how Newton’s inductive argument of the Principia can be defended against criticisms leveled against it by Duhem, Popper and myself. I argue that Duhem’s and Popper’s criticisms can be countered, but mine cannot. It requires that we reconsider, not just Newton’s inductive argument in the Principia, but also the nature of science more generally. The methods of science, whether conceived along inductivist or hypothetico-deductivist lines, make implicit metaphysical presuppositions which rigorously require us to make them explicit within science so that they can be critically assessed, alternatives being developed and assessed, in the hope that they can be improved. Despite claiming to derive his law of gravitation by induction from phenomena without resource to hypotheses, Newton does nevertheless acknowledge in the Principia that his rules of reasoning make metaphysical presuppositions. To this extent, Newton has a more enlightened view of scientific method than most 20th and 21st century scientists and historians and philosophers of science.
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