Application of SRMS 154 as Sustained Release Matrix for the Delivery of Stavudine: In vitro and in vivo Evaluation and Effect of Poloxamer 188 on the Properties of the Tablets.

BACKGROUND: Stavudine is an antiretroviral therapy with so many side effects and has a short half-life of 1.5 h. It degrades to thymine under hydrolytic, oxidative and photolytic conditions hence has major formulation challenges. OBJECTIVES: To formulate sustained release lipid based stavudine and to study the properties of the formulations by in vitro and in vivo methods. METHODS: Stavudine tablets were formulated by moulding using validated tablets moulds. The carrier used were solidified reverse micellar solution (SRMS) made up of varying ratios of hydrogenated palm oil and Phospholipid admixtures. Evaluation tests were carried out on the tablets using both Pharmacopoeial and non Pharmacopoeial test. Drug release was studied in both simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.2). In vivo release was studied using Wistar rats. RESULTS: The results showed that stavudine tablets exhibited weight range of 372 ± 0.14 to 386 ± 0.52 mg, friability ranged from 0.00 to 0.13 % and hardness ranged from 4.27 ± 0.25 to 5.30 ± 0.21 Kgf. Tablets formulated with SRMS 1:2 had erosion time range of 60.80 ± 1.23 to 87.90 ± 2.33 min and was affected significantly by the presence of Poloxamer 188 (p < 0.05). The formulations exhibited T100 % at 10 to13 h in SIF. Stavudine tablets showed the area under the curve (AUC) of 854.0 µg/h/ml, significantly higher than the AUC of the reference (p < 0.05). CONCLUSION: Stavudine SRMS-based tablets had good stability and sustained release properties. Formulations containing 1 % Poloxamer 188 exhibited enhanced in vivo absorption and hence could be used once daily in order to enhance the bioavailability of this drug.

Formulation in vitro and in vivo evaluation of SRMS-based heterolipid-templated homolipid delivery system for diclofenac sodium.

The sole objective of this work was to design successful dosage oral forms of diclofenac sodium (DiNa)-loaded solid lipid microparticles (SLM) based on solidified reverse micellar solution (SRMS). Hot homogenization technique was employed to prepare DicNa SLM using a mixture goat fat and Phospholipon® 90 G as lipid matrix and Tween®-80 as mobile surfactant. Characterization based on percentage yield, morphology, particle size, zeta potential, percentage encapsulation, pH and stability of SLMs were investigated. Anti-inflammatory, gastrointestinal tract (GIT) sparing effect and pharmacokinetics were carried out in rat model after oral administration. Results showed that the SLMs were spherical and smooth. The optimized formulation (SLM-4) had particle size of 79.40 ± 0.31 µm, polydispersity index of 0.633 ± 0.190, zeta potential of -63.20 ± 0.12 mV and encapsulation efficiency of 91.2 ± 0.1% with good stability after 8 months of storage. The DicNa SLM had sustained release effect with good anti-inflammatory activity. Higher and prolonged plasma DicNa concentration was shown by the SLM-4 compared to pure drug and a conventional sample. These studies demonstrate that DicNa-loaded SLM based on SRMS could be a promising oral formulation for enhanced bioavailability, pharmacologic activity and gastrointestinal sparing effect of the NSAID, DicNa.

Formulation development and evaluation of the anti-malaria properties of sustained release artesunate-loaded solid lipid microparticles based on phytolipids.

UNLABELLED: CONTEXTS: Artemisinins and its derivatives are considered the basis in the treatment of Plasmodium falciparum malaria due to their high potency and rapid action. However, they have short half life, low solubility, and poor oral bioavailability, hence the need to formulate sustained release lipid particulate dosage form of these drugs. OBJECTIVES: To formulate and evaluate artesunate-loaded solid lipid microparticles (SLMs) based on structured lipid matrices consisting of soybean oil and dika wax. MATERIALS AND METHODS: The lipid matrices were characterized by differential scanning calorimetry (DSC), small-angle X-ray diffraction (SAXD), and wide-angle X-ray diffraction (WAXD). The SLMs were prepared by hot melt-homogenization. Time-dependent particle size analysis, time-dependent pH stability studies, encapsulation efficiency (EE%), and in vitro drug release were carried out on the SLMs. In vivo anti-malarial studies were performed using a modified Peter's 4-day suppressive protocol using Plasmodium berghei infected mice. RESULTS AND DISCUSSION: Thermograms of the lipid matrices showed modifications in the microstructure of dika wax as a result of inclusion of soybean oil. SAXD and WAXD diffractograms showed that the lipid matrices were found to be non-lamellar. Particle size of SLM increased with time, while the pH was almost constant. The SLMs had maximum EE% of 80.6% and sustained the release of artesunate more than the reference tablet. In vivo pharmacodynamic studies showed that the SLMs had significant (p < 0.05) reduction in parasitaemia compared with reference tablet. CONCLUSION: Artesunate-loaded SLMs could be used once daily in the treatment of malaria.

Pharmacodynamics of diclofenac from novel Eudragit entrapped microspheres.

Effective clinical utilization of non-steroidal anti-inflammatory drugs such as diclofenac sodium (DS) is significantly limited by their ulcerogenic potential and poor bioavailability after oral administration, thus necessitating the need for a better carrier to minimize these obvious limitations. The objective of this study was to evaluate Eudragit® RS100/RL100 microspheres formulated by the solvent-evaporation technique for improved delivery of diclofenac. Three batches of (DF1, DF2 and DF3) microspheres were prepared using different ratios of Eudragit RS-100 and RL-100 polymers based on the solvent-evaporation method. The microspheres were characterized based on morphological properties, particle size analysis and encapsulation efficiency (EE%). In vitro release of DS was investigated in both 0.1 N HCl (pH 1.2) and phosphate-buffered saline (pH 7.4), while anti-inflammatory studies were evaluated in the rat model. Maximum EE% of 86.61 ± 0.11, 88.14 ± 0.16 and 85.50 ± 0.21 was obtained for DF1, DF2 and DF3, respectively. Discrete, smooth and brownish microspheres of size range 437 ± 0.01-479 ± 0.21 µm were obtained. Release of DS from the formulation depends on the polymer ratio. All the batches exhibited good anti-inflammatory activities. Microsphere formulations based on Eudragit® polymers would likely offer a reliable and alternative means of delivering DS orally.

Analgesic and Micromeritic evaluations of SRMS-based oral Lipospheres of Diclofenac Potassium.

The objective of our work was to study the micromeritic properties of lyophilized diclofenac potassium-loaded lipospheres and to evaluate in vivo, the analgesic properties of diclofenac potassium in the lipospheres in addition to other in vitro properties. Solidified reverse micellar solutions were prepared by fusion using 1:1, 2:1, and 1:2% w/w of Phospholipon(®) 90H and Softisan(®) 154. Diclofenac potassium (1, 3, and 5% w/w) was incorporated into the solidified reverse micellar solutions. Solidified reverse micellar solutions-based lipospheres were formulated by melt homogenization techniques using Ultra-Turrax homogenizer, and thereafter lyophilized to obtain water-free lipospheres. The lipospheres were characterized in terms of particle size and morphology, stability, thermal analysis, drug content, encapsulation efficiency, and loading capacity. The flow properties of the lipospheres were studied using both direct and indirect methods of assessing flow. The analgesic properties of the lipospheres were studied using the hot plate method. Results obtained showed that the yield of diclofenac potassium-loaded lipospheres was high and the particle size ranged from 0.61±0.07 to 2.55±0.04 µm. The lipospheres had high encapsulation efficiency of 95%, which was affected by the amount of drug loaded, while the loading capacity increased with the increase in drug loading. Diclofenac potassium-loaded lipospheres exhibited poor flow. The formulations exhibited good analgesic effect compared with the reference and had 84 to 86% drug release at 13 h. The lipospheres based on solidified reverse micellar solutions could be used for oral delivery of diclofenac potassium.

Formulation and evaluation of novel solid lipid microparticles as a sustained release system for the delivery of metformin hydrochloride.

The low encapsulation efficiency of conventional solid lipid microparticles (SLMs) especially for hydrophilic drugs has remained a challenge to drug formulation experts. This work seeks to address the issue of inefficient delivery of metformin hydrochloride (MTH), a potent hydrophilic oral antihyperglycemic agent, using novel SLMs based on solidified reverse micellar solutions (SRMS) prepared by melt-emulsification using a lipid derived from Capra hircus and Phospholipon® 90H. Characterization based on size, morphology, zeta potential, polydispersity index, encapsulation efficiency (EE%), loading capacity (LC) and time-resolved stability were carried out on the SLMs. The in vitro release of MTH from the SLMs was performed in phosphate buffer (pH 7.4) while the in vivo antidiabetic properties were investigated in alloxan-induced diabetic rats. Stable, spherical and smooth SLMs were obtained. Loading of MTH into the SLMs had no effect on the surface charge of the particles. The SLMs with 1.0%w/w PEG 4000 resulted in significantly (p < 0.05) higher EE% while those with 2.0%w/w gave the least. The LC values ranged from 20.3 to 29.1 and 14.6 to 24.1 for SLMs containing 500 mg and 250 mg of MTH, respectively. The in vitro release studies revealed significant release of MTH from the SLMs whereas the in vivo antidiabetic studies indicated that novel SLMs containing 500 mg of MTH gave significantly (p < 0.05) higher glucose reduction than glucophage®. This research has shown that SLMs based on SRMS offer a new and better approach of delivering MTH, thus encouraging further development of this formulation.

Transdermal microgels of gentamicin.

Phospholipid-modified solid lipid microparticles (SLMs) of Phospholipon® 90G and 90H encapsulating the hydrophilic drug, gentamicin were produced and loaded into three polymeric hydrogels of Poloxamer 407 and polyacrylic acids (Carbopols® 971P and 974P). The SLMs were characterized by morphology and particle size, drug encapsulation efficiency, thermal properties, pH, and storage stability, whereas the microgels were evaluated for viscosity, spreadability, pH, drug content, and in vitro antimicrobial drug release against five microorganisms (Klebsiella spp., Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa). Our results generally showed Poloxamer 407 microgels of P90H and P90G as having the most desirable properties in terms of fast antibacterial activity on all tested microorganisms, in vitro diffusion-dependent permeation through rat abdominal skin, spreadability, pH, and viscosity, superior to polyacrylic acids microgels.

Preliminary evaluation of the immunoenhancement potential of Newcastle disease vaccine formulated as a cationic liposome.

This study evaluates the enhancement of immune response of birds to Newcastle disease (ND) vaccine encapsulated in 1,2-dioleoyl-3-trimethylammonium propane (DOTAP)-based liposomes. The vesicles of the liposomal ND vaccine were physically characterized for shape, particle size and zeta potential. The results of the analyses showed that vesicles of the liposomal ND vaccine were spherical and tightly packed. The mean size distribution was below 100 nm. The mean zeta potential was 24 mV. Sixty experimental birds were then divided into an unvaccinated group, a liposomal ND vaccine group and a live La Sota(®) vaccine group. Both the liposomal ND vaccine and live La Sota(®) vaccine groups were vaccinated orally at 3 and 6 weeks of age. The mean antibody titres, total and differential white blood cell count, and blood chemistry, respectively, were assessed. Ten birds from each group were challenged by oral administration of 0.2 ml virulent Herts 33 strain at 9 weeks of age. The log(2) mean antibody titre induced by the liposomal ND vaccine after secondary immunization of the birds was 9.60±0.95 while that of the live La Sota( (®) ) vaccine was 6.00±0.63. Nine of the 10 challenged birds in the unvaccinated group died while none died from the liposomal ND vaccine group or the live La Sota(®) vaccine group. After the boost vaccination, the chickens vaccinated with the liposomal ND vaccine had a higher mean antibody titre, indicating that encapsulating ND vaccine in DOTAP-based liposome induced significantly higher immunity than the live La Sota(®) vaccine.

Antagonistic antimalarial properties of pawpaw leaf aqueous extract in combination with artesunic acid in Plasmodium berghei-infected mice.

BACKGROUND & OBJECTIVES: Artemisinins, the main stay in the treatment of malaria are used in combinations with other antimalarials to forestall resistance, as artemisinin-combination therapies (ACTs). However, ACTs are expensive and some of the non-artemisinin components are not well-tolerated by patients. There are several folkloric and scientific proofs of the efficacy of herbal remedies for malaria. Mature leaves of Carica papaya is widely used to treat malaria in several African countries. An ACT involving a medicinal herb extract or its active constituent(s) will provide an indigenous alternative/herbal ACT. METHODS: Mature fresh leaves of Carica papaya were grounded and macerated in cold distilled water for 24 h and the extract (PCE) was stored in the refrigerator for seven days. Fresh extracts were made as needed. The antiplasmodial activity of PCE and/or artesunic acid were determined by using the Peter's 4-day suppressive test in Plasmodium berghei-infected mice. The ED50 and ED90 were calculated from the dose-response relationships. RESULTS: The combination of 50 mg/kg of PCE and 15 mg/kg of artesunic acid produced a significant reduction of parasitemia (81.25%), compared to 50 mg/kg PCE alone (37.7%). The mean survival time of the combinations of PCE and 15 mg/kg of artesunic acid, and PCE alone followed a dose-dependent manner. The ED50 of PCE showed that it has a very good activity. The isobolar equivalent (IE) calculated from the ED90 of PCE in combination with artesunic acid showed that the interaction was antagonistic. INTERPRETATION & CONCLUSION: Although pawpaw alone was found to have a very good activity, its combination with artesunic acid is antagonistic. Combinations of artemisinins and pawpaw show little promise for combination therapy development.

Formulation and evaluation of niosomes.

Span 20-based niosome was prepared by lipid film hydration technique and loaded with Newcastle disease vaccine. Three batches with Span 20, cholesterol and dicetyl phosphate in micro molar ratios of 10:10:1; 15:15:1 and 20:20:1 were prepared and evaluated for encapsulation efficiency using haemagglutination test. The morphology of the vesicles was studied by means of transmission electron microscopy. Particle size, zeta potential and polydispersity index were determined by photon correlation spectroscopy using a nanosizer. Adjuvanticity was assessed using haemagglutination inhibition test. The vesicles of Span 20-based niosomes were distinct, near spherical large unilamellar vesicles. The vesicles were of varied sizes (<1000 nm) with the entrapped Newcastle disease vaccine in the core of the vaccine. The zeta potential had a peak at -50 mV. The polydispersity index was 0.68. Haemagglutination inhibition test showed a 71% increment in immune response over that of the marketed La Sota(®) vaccine which had a 60% increment in immune response. The niosomal vaccine did not alter but rather enhanced the immunogenicity of the Newcastle disease vaccine.

SRMS142-based solid lipid microparticles: application in oral delivery of glibenclamide to diabetic rats.

P90Gylation refers to the modification of lipid molecules by one or more phospholipid chains. Phospholipon 90G (P90G) contains about 94.0% of phosphatidylcholine stabilized with 0.1% ascorbyl palmitate and is a safe (GRAS) FDA-approved parenteral excipient with wide applications in drug delivery. P90Gylated-Softisan 142 conjugate, otherwise referred to as (SRMS142), has numerous advantages: wetting, solubilization, drug stabilization, emulsification, and modified release. Here, we report an evaluation of solid lipid microparticles (SLMs) formulated from SRMS142 systems as an alternative carrier system for oral glibenclamide administration in diabetic rats. The result of our findings showed that SRMS142 generated an imperfect matrix with numerous spaces that accommodated glibenclamide in a concentration-dependent manner up to 60.58%. The blood glucose-lowering effect of the SLMs was higher than that of a commercial sample.

Sustained release and permeation of timolol from surface-modified solid lipid nanoparticles through bioengineered human cornea.

PURPOSE: The aim of the study was to formulate and evaluate surface-modified solid lipid nanoparticles sustained delivery system of timolol hydrogen maleate, a prototype ocular drug using a human cornea construct. MATERIALS AND METHODS: Surface-modified solid lipid nanoparticles containing timolol with and without phospholipid were formulated by melt emulsification with high-pressure homogenization and characterized by particle size, wide-angle X-ray diffraction, encapsulation efficiency, and in vitro drug release. Drug transport studies through cornea bioengineered from human donor cornea cells were carried out using a modified Franz diffusion cell and drug concentration analyzed by high-performance liquid chromatography. RESULTS: Results show that surface-modified solid lipid nanoparticles possessed very small particles (42.9 +/- 0.3 nm, 47.2 +/- 0.3 nm, 42.7 +/- 0.7 nm, and 37.7 +/- 0.3 nm, respectively for SM-SLN 1, SM-SLN 2, SM-SLN 3, and SM-SLN 4) with low polydispersity indices, increased encapsulation efficiency (> 44%), and sustained in vitro release compared with unmodified lipid nanoparticles whose particles were greater than 160 nm. Permeation of timolol hydrogen maleate from the surface-modified lipid nanoparticles across the cornea construct was sustained compared with timolol hydrogen maleate solution in distilled water. CONCLUSIONS: Surface-modified solid lipid nanoparticles could provide an efficient way of improving ocular bioavailability of timolol hydrogen maleate.

Formulation and in vitro evaluation of a PEGylated microscopic lipospheres delivery system for ceftriaxone sodium.

The aim of this study was to formulate and evaluate in vitro, ceftriaxone sodium lipospheres dispersions for oral administration. Ceftriaxone sodium lipospheres were prepared by melt-emulsification using 30%w/w Phospholipon 90H in Softisan 154 as the lipid matrix containing increasing quantities of PEG 4000 (10, 20, 30, and 40%w/w). Characterization based on particle size, particle morphology, encapsulation efficiency, loading capacity and pH were carried out on the lipospheres. Microbiological studies of the ceftriaxone sodium-loaded lipospheres were performed using Escherichia coli as the model organism. In vitro permeation of ceftriaxone sodium from the lipospheres through artificial membrane (0.22 microm pore size) was carried out using Franz cell and simulated intestinal fluid (SIF) without pancreatin as acceptor medium. Photomicrographs revealed spherical particles within a micrometer range with minimal growth after 1 month (Maximum size = 64.76 +/- 3.81 microm). Microbiological studies indicated that lipospheres formulated with 20%w/w of PEG 4000 containing 2%w/w or 3%w/w of ceftriaxone sodium gave significantly (p < 0.05) higher inhibition zone diameter than those with 30%w/w or 40%w/w of PEG 4000. The result also indicated that lipospheres with 10%w/w PEG 4000 resulted in significantly higher encapsulation efficiency (p < 0.05) while those with 30%w/w gave the least, while the loading capacity values ranged from 3.22 mg of ceftriaxone sodium/100 mg of lipid to 6.36 mg of ceftriaxone sodium/100 mg of lipid. Permeation coefficient values varied and ranged from 8.55 x 10(-7) cm/s to 2.08 x 10(-6) cm/s depending on the concentration of PEG 4000. The result of this study gave insight that the issue of ceftriaxone stability in oral formulation could be adequately addressed by tactical engineering of lipid drug delivery systems such as lipospheres.

Evaluation of the pharmacodynamic activity of insulin from bilosomal formulation.

In this study, bilosome as a drug delivery system for insulin was studied. Two bilosomal preparations were formulated and assessed. One was prepared using a lipid extract from Soya beans seed (SBE), Palmitic acid (PA) and cholesterol (CH ) in the ratio of 0.25:1:1 w/w designated as BI while the other (BII) contained PA and CH as the lipid entity at the ratio of 1:1 w/w. Each of the preparations contained 0.5% of sodium deoxycholate (SDC) and soluble insulin. BI was given orally only, while BII was administered subcutaneously, intraperitoneally and orally to different groups of streptozotocin-induced diabetic male rats, and the blood glucose levels were measured at predetermined time intervals. The results of the studies showed that oral administration of BI and BII produced blood glucose reduction, which could mimick endogenous release of insulin with prolonged activity, although, less blood sugar lowering compared with parental administration. BI (oral I) containing SBE had greater reduction of blood glucose than BII (oral II) ,showing that SBE increased the bioavailability of insulin. Bilosomal insulin formulation could provide a good oral delivery system for insulin that would affect the entero-insular axis similar to endogenous insulin.

Polyelectrolyte complexes of Eudragit l30 d-55 and gelatin: antinociceptive activity of entrapped piroxicam.

The electrostatic interaction between oppositely charged polyelectrolytes leads to the formation of polyelectrolyte complexes, which are of considerable interest because of their potential applications as both drug carriers or surface modifying agents. In this study, in vitro and in vivo studies were carried out on polyelectolyte complexes formulated with Eudragit L30 D-55 and gelatin. The complexes of Eudragit L30 D-55 and gelatin were formulated by nonstoichiometric method. The polyelectrolyte complexes formulated were then granulated and evaluated by percentage yield, particle size, and swelling behavior. The pharmacodynamic effects of piroxicam entrapped in the complexes were determined using healthy rats. Results showed that gelatin and Eudragit L30 D-55 formed polyelectrolyte complexes that prolonged the antinociceptive effects of piroxicam in experimental rats. The performance of the polyelectrolyte complexes could be stated in the following descending rank order: 1:1 > 2:1 > 1:2 ratios of Eudragit L30 D-55 and gelatin. Nonstoichiometric interactions of gelatin and Eudragit L30 D-55 could yield matrices with adequate characteristics for the formulation of sustained release systems of drugs.

Solid lipid nanodispersions containing mixed lipid core and a polar heterolipid: characterization.

This paper describes the characterization of solid lipid nanodispersions (SLN) prepared with a 1:1 mixture of theobroma oil and goat fat as the main lipid matrix and Phospholipon 90G (P90G) as a stabilizer heterolipid, using polysorbate 80 as the mobile surfactant, with a view to applying the SLN in drug delivery. The 1:1 lipid mixture and P90G constituting the lipid matrix was first homogeneously prepared by fusion. Thereafter, the SLN were formulated with a gradient of polysorbate 80 and constant lipid matrix concentration by melt-high pressure homogenisation. The SLN were characterized by time-resolved particle size analysis, zeta potential and osmotic pressure measurements, differential scanning calorimetry (DSC) and wide angle X-ray diffraction (WAXD). Transmission electron microscopy (TEM) and isothermal heat conduction microcalorimetry (IMC) which monitors the in situ crystallization were also carried out on the SLN containing P90G and 1.0 % w/w of polysorbate 80. The results obtained in these studies were compared with SLN prepared with theobroma oil with and without phospholipid. Particle size analysis of SLN indicated reduction in size with increase in concentration of mobile surfactant and was in the lower nanometer range after 3 months except SLN prepared without P90G or polysorbate 80. The lipid nanoparticles had negative potentials after 3 months. WAXD and DSC studies revealed low crystalline SLN after 3 months of storage except in WAXD of SLN formulated with 1.0 % w/w polysorbate 80. TEM micrograph of the SLN containing 1.0 % w/w polysorbate 80 revealed discrete particles whose sizes were in consonance with the static light scattering measurement. In situ crystallization studies in IMC revealed delayed crystallization of the SLN with 1.0 % w/w polysorbate 80. Results indicate lipid mixtures produced SLN with lower crystallinity and higher particle sizes compared with SLN prepared with theobroma oil alone with or without P90G, and would lead to higher drug incorporation efficiency when used in formulation of actives. Mixtures of theobroma oil and goat fat would be suitable for the preparation of nanostructured lipid carriers. SLN of theobroma oil containing phospholipid could prove to be a good ocular or parenteral drug delivery system considering the low particle size, particle size stability and in vivo tolerability of the component lipids. SLN prepared with lipid admixture, which had higher increase in d(90%) on storage are suitable for preparation of topical and transdermal products.

Investigation of surface-modified solid lipid nanocontainers formulated with a heterolipid-templated homolipid.

There is increasing interest in the search for improved drug delivery systems with greater versatility. Consequently, many drug delivery systems have been studied. In this study, surface-modified lipid nanocontainers were formulated with a homolipid from Capra hircus (goat fat) templated with a heterolipid (Phospholipon 90G) which was also the surface modifier. The solid lipid nanocontainers (SLN) were formulated by hot high pressure homogenisation using increasing concentrations of polysorbate 80 as the mobile surfactant. Prior to SLN preparation, the templated homolipid was formulated by fusion to obtain a homogeneous lipid matrix, which was characterized using differential scanning calorimetry (DSC), polarized light microscopy (PLM) and wide angle X-ray diffraction (WAXD) to obtain its thermal and crystal characteristics. Isothermal heat conduction microcalorimetry (IMC) and freeze-fracture transmission electron microscopy (FFTEM) studies were carried out on the templated homolipid and SLN containing 1.0% (w/w) of polysorbate 80 to study their in situ crystallization kinetics and morphology, respectively. The formulated SLN were also subjected to time-resolved DSC, WAXD and particle size analyses for one month. The thermal and crystal characteristics were compared with those of the bulk lipid matrix (templated homolipid). Result of the particle size analysis indicated that the particles size remained roughly within the lower nanometer range after one month. FFTEM micrograph of the lipid matrices revealed lamellar sheets for Phospholipon 90G and layered triglyceride structures for the homolipid and Phospholipon 90G-templated homolipid. FFTEM micrograph of SLN revealed anisometric structures. PLM of the templated homolipid did not show, but goat fat (homolipid) alone showed slight growth in crystals with time. WAXD and DSC studies revealed minor increase in crystallinity of the new lipid matrix after one month and DSC also detected templation of homolipid by the heterolipid noted by the disappearance of the lower melting peak of the homolipid. However, for the SLN, WAXD results showed low crystalline particles while DSC only showed a very little endothermic process after one month of storage at 20 degrees C. The implication of this finding is that progression of the SLN to highly ordered particles over time would not occur. This will be favourable for any incorporated drug as drug expulsion, due to increase in crystallinity, will not occur. Result obtained from analysis of the isothermal crystallization exotherms indicated that the templated homolipid and SLN1 containing 1.0% polysorbate 80 possess similar nucleation mechanisms and growth dimensions different from the pure homolipid. The SLN containing 0.5 and 1.0% polysorbate 80 possessed good properties and could prove to be good delivery systems for drugs for parenteral or ocular administration. The result of this study also shows a method of improving natural lipids for use in particulate drug delivery systems.

Further characterization of theobroma oil-beeswax admixtures as lipid matrices for improved drug delivery systems.

There is an increasing interest in lipid based drug delivery systems due to factors such as better characterization of lipidic excipients and formulation versatility and the choice of different drug delivery systems. It is important to know the thermal characteristics, crystal habit, texture, and appearance of a new lipid matrix when determining its suitability for use in certain pharmaceutical application. It is line with this that this research was embarked upon to characterize mixtures of beeswax and theobroma oil with a view to applying their admixtures in drug delivery systems such as solid lipid nanoparticles and nanostructured lipid carriers. Admixtures of theobroma oil and beeswax were prepared to contain 25% w/w, 50% w/w, and 75% w/w of theobroma oil. The admixtures were analyzed by differential scanning calorimetry (DSC), small angle X-ray diffraction (SAXD), wide angle X-ray diffraction (WAXD), and isothermal heat conduction microcalorimetry (IMC). The melting behavior and microstructures of the lipid admixtures were monitored by polarized light microscopy (PLM). Transmission electron microscopy (TEM) was used to study the internal structures of the lipid bases. DSC traces indicated that the higher melting peaks were roughly constant for the different admixtures, but lower melting peaks significantly increased (p < 0.05). The admixture containing 25% w/w of theobroma oil possessed highest crystallinity index of 95.6%. WAXD studies indicated different reflections for the different lipid matrices. However, new interferences were detected for all the lipid matrix admixtures between 2theta = 22.0 degrees and 2theta = 25.0 degrees. The lipid matrices containing 50% w/w and 25% w/w of theobroma oil showed absence of the weak reflection characteristic of pure theobroma oil, while there was disappearance of the strong intensity reflection of beeswax in all the lipid matrix admixtures at all stages of the study. PLM micrographs revealed differences with regard to the thermal and optical behaviors depending on the composition of the matrix. The lipid matrix consisting of 75% w/w of theobroma oil showed a spherulite texture after 4 weeks of isothermal storage. Crystallization exotherms of lipid matrices containing 50% w/w and 25% w/w of theobroma oil showed change in modification after 30 min with the latter having a greater time-dependent crystallization. Generally, low non-integral Avrami exponents and growth rate constants were obtained for all the lipid matrices, with the admixture containing 25% w/w theobroma oil having the lowest Avrami exponent and growth rate constant. Based on the results obtained, admixtures containing 50% w/w and 75% w/w of theobroma oil could be applied in the formulation of solid lipid nanoparticles and nanostructured lipid carriers as these lipid matrices possessed crystal characteristics that favour such drug delivery systems.

A critical study of novel physically structured lipid matrices composed of a homolipid from Capra hircus and theobroma oil.

There is increasing interest in drug formulation using lipids. In this study, some physically structured lipid matrices were formulated and characterized for drug delivery applications. Lipid matrices containing a novel homolipid from Capra hircus (goat fat) and theobroma oil, at 25, 50 and 75% (w/w) concentration of the homolipid were formulated by fusion. The lipid matrices were subjected to some characterization procedures such as differential scanning calorimetry (DSC) to ascertain their supramolecular properties, small angle X-ray diffraction (SAXD), wide angle X-ray diffraction (WAXD), polarized light microscopy (PLM) and isothermal heat conduction microcalorimetry (IMC). The internal structures of some selected lipid matrices were also studied by freeze-fracture transmission electron microscopy (FFTEM). DSC results obtained indicated that goat fat has a pre-transition at 15.9 +/- 0.2 degrees C (after 1 week) and melts completely with two detectable melting peaks at 33.0 +/- 0.2 and 49.9 +/- 0.1 degrees C, and total enthalpy of 99.9 +/- 2.5 mJ/mg determined after 6 weeks of preparation. The melting enthalpy of goat fat changed after 3 weeks but remained constant after 6 weeks while the melting enthalpy of the lipid matrix containing 50% (w/w) goat fat changed after 3 and 6 weeks. An increase in lower melting peak was observed in the lipid matrix containing 25% (w/w) goat fat after 6 weeks. WAXD and SAXD of the physically structured lipid matrices showed reflections of the different pure lipids but new interferences were detected in WAXD mostly between 2theta=17.5 degrees and 2theta=27.5 degrees . PLM observation revealed the presence of Maltese crosses for the homolipid at 37 degrees C, which disappeared upon heating at 51.0 degrees C. PLM of the structured lipid matrix containing 25% (w/w) goat fat showed distinct crystal growth after 4 weeks among the admixtures. However, IMC studies did not reveal any change in recrystallization behaviour in this lipid matrix within 24 h. Analysis of the crystallization exotherms indicated that the lipid matrix containing 50% (w/w) goat fat showed unique crystallization kinetics and possessed the lowest Avrami exponent, while goat fat alone showed slight change within the first 45 min of isothermal crystallization. Physically structured lipid matrix containing 75% (w/w) goat fat possessed the lowest growth rate constant.

Pharmacodynamics of piroxicam from self-emulsifying lipospheres formulated with homolipids extracted from Capra hircus.

A self-emulsifying system is a mixture of oil and surfactant that forms oil-in-water emulsion when exposed to aqueous fluid. It enhances the in vitro dissolution and improves the in vivo absorption of lipophilic drugs that have poor aqueous solubility. In this study, a poorly water soluble drug, piroxicam, was incorporated into self-emulsifying lipospheres consisting of a mixture of a homolipid from Capra hircus and Tween 65. Various solid self-emulsifying lipospheres were formulated having different ratios of the homolipid and Tween 65 to contain piroxicam. The self-emulsifying lipospheres were evaluated using the following parameters: particle size, absolute drug content, and dissolution profile. The pharmacodynamics of the drug from the lipospheres were also evaluated using antinociceptive activity on albino mice. Based on our results the self-emulsifying lipospheres containing 4:11 ratio of the homolipid and Tween 65 had the best performance in terms of antiinflammatory effect, particle size, and dissolution. They possibly could be employed in the formulation of self-emulsifying lipospheres for various administration.