Development and Evaluation of PEG-Gelatin-Based Microparticles to Enhance the Oral Delivery of Insulin.

BACKGROUND: Diabetes mellitus is a global disease identified by hyperglycemia due to defects in insulin secretion, insulin action, or both. OBJECTIVE: The main objective of this research was to evaluate the ability of gelatinized Poly(ethylene glycol) (PEG) microparticles to be used as carriers for oral insulin delivery via double emulsion preparation. METHODS: Five different batches of the formulation consisting of gelatin:PEG were prepared as follows: 0:1 (W1), 1:0 (W2), 1:1 (W3), 1:3 (W4), and 3:1 (W5). The prepared microparticles (from insulin-loaded batches) had particle sizes ranging from 19.5 ± 0.32-23.9 ± 0.22 µm and encapsulation and loading capacities ranging from 78.8 ± 0.24-88.9 ± 0.95 and 22.2 ± 0.96-29.7 ± 0.86%, respectively. The minimum and maximum in vitro release rates were 8.0 and 66.0%, respectively, for batches W1 and W2 at 8 h. RESULTS: Insulin-loaded MPs induced a significant decrease in glucose levels, with a reduction from 100 to 33.35% in batch W5 at 9 h compared to that of subcutaneous insulin (100 to 22.63%). A liver function study showed that the formulation caused no obvious toxicity to the experimental rats. CONCLUSION: Gelatinized PEG-based microparticles as insulin delivery systems may open a new window into the development of oral insulin for diabetic treatment.

Retraction notice to "Mechanistic insight into the bioactivity of prodigiosin-entrapped lipid nanoparticles against triple-negative breast, lung and colon cancer cell lines" [Heliyon 9 (2023) e16963].

[This retracts the article DOI: 10.1016/j.heliyon.2023.e16963.].

Mechanistic insight into the bioactivity of prodigiosin-entrapped lipid nanoparticles against triple-negative breast, lung and colon cancer cell lines.

This research investigates the potentials of prodigiosin(PG) derived from bacteria and its formulations against triple-negative breast (TNB), lung, and colon cancer cells. The PG was extracted from S. marcescens using continuous batch culture, characterized, and formulated into lyophilized parenteral nanoparticles (PNPs). The formulations were characterized with respect to entrapment efficiency (EE), DSC, FT-IR, TEM, and proton nuclear magnetic resonance (1H NMR) spectroscopy. In vitro drug release was evaluated in phosphate buffer (pH 7.4) while acute toxicity, hematological and histopathological studies were performed on rats. The in vitro cytotoxicity was evaluated against TNB (MCF-7), lung (A-549), and colon (HT-29) cancer cell lines. High EE (92.3 ± 12%) and drug release of up to 89.4% within 8 h were obtained. DSC thermograms of PG and PG-PNPs showed endothermic peaks indicating amorphous nature. The FT-IR spectrum of PG-PNPs revealed remarkable peaks of pure PG, indicating no strong chemical interaction between the drug and excipients. The TEM micrograph of the PG-PNPs showed nano-sized formulations (20-30 nm) whose particles were mostly lamellar and hexagonal structures. The 1H NMR result revealed the chemical structure of PG showing all assigned proton chemical shifts. Toxicity results of the PG and its formulation up to a concentration of 5000 mg/kg showed insignificant vacuolar changes of hepatocytes in the liver, with normal renal medulla and cortex in the kidney. The PG and PG-PNPs inhibited the growth of breast, lung, and colon cell lines. The nano-sized lipid formulation (PG-PNPs) showed potential in PG delivery and cancer treatments.

Exploitation of capsule system for colon targeted drug delivery of biopolymer-based microparticles: in vivo and in vitro applications.

The current study was to improve and control aceclofenac delivery prepared as biopolymer-based microparticles for effective colon-targeted drug delivery using modified gelatin capsules (MGCs) at different time intervals developed in two batches (C1 and C2). Microparticles were formulated with extracted mucuna gum using liquid paraffin oil (AC.LPO) and soybean oil (AC.SO) and evaluated in vitro for physicochemical performance and in vivo in rats. Encapsulation efficiency ranges from 54.48 ± 0.21% to 82.83 ± 0.22% for AC.LPO and 52.64 ± 0.11% to 80.36 ± 0.22% for AC.SO. SEM showed oblong and irregular shapes with porous and cracked surfaces. DSC showed low enthalpy and a very broad endothermic peak depicting high amorphous property. Delayed drug release was observed in the upper gastrointestinal tract with sustained release depicted in the lower gastrointestinal tract (GIT) using 3 and 9-h batch C1 of MGCs. AC.SO exhibited significantly (p < 0.05) higher anti-inflammatory activity (86%) than AC.LPO (77%). Hence, aceclofenac colon delivery could be improved and controlled using biopolymer-based colon-targeted microparticles delivered with MGCs.

Formulation and evaluation of transdermal nanogel for delivery of artemether.

Artemether (ART) is second to artesunate in being the most widely used derivatives of artemisinin in combination therapy of malaria. Nanostructured lipid carrier (NLC) formulations were prepared following our previous report using optimized ART concentration of 0.25 g dissolved in 5% w/v mixture of solid (Gelucire 43/01 and Phospholipon 85G) and liquid (Transcutol) lipids at 90 °C. An aqueous surfactant phase at 90 °C was added (dropwise) under magnetic stirring (1000 rpm) for 5 min. The pre-emulsion was speedily homogenized at 28,000 rpm for 15 min and further probe sonicated at 60% amplitude (15 min). Resultant sample was cooled at room temperature and frozen at - 80 °C prior to lyophilization. The freeze-dried sample was used for solid-state characterization as well as in the formulation of transdermal nanogels using three polymers (Carbopol 971P, Poloxamer 407, and Prosopis africana peel powder) to embed the ART-NLC, using ethanol as a penetration enhancer. Transdermal ART-nanogels were characterized accordingly (physical examination, pH, drug content, rheology, spreadability, stability, particle size and morphology, skin irritation, in vitro and ex vivo skin permeation, and analysis of permeation data), P < 0.05. Results indicated that ART nanogels showed good encapsulation, drug release, pH-dependent swelling, stability, and tolerability. Overall, ART nanogels prepared from Poloxamer 407 showed the most desirable drug permeation, pH, swellability, spreadability, viscosity, and transdermal antiplasmodial properties superior to PAPP-ANG > C971P-ANG. A two-patch/week concurrent application of the studied nanogels could offer 100% cure of malaria as a lower-dose (50 mg ART) patient-friendly regimen devoid of the drug's many side effects.

Insulin-loaded mucoadhesive nanoparticles based on mucin-chitosan complexes for oral delivery and diabetes treatment.

In this study, insulin-loaded nanoparticles (NPs) were prepared via self-gelation method using chitosan and aqueous soluble snail mucin as natural polymers. Herein, mucins were ionically interacted with chitosan at different concentrations to obtained insulin-loaded NPs, labelled as A1 (1:1) (i.e., chitosan 2 % w/v + mucin 2 % w/v) and A2 (2:1) (chitosan 4 % w/v + mucin 2 % w/v), using poloxamer and poly vinyl alcohol as solid surfactant. Such formulation was selected to provide the necessary dynamics for the formation of the nanoparticles while maintaining the surface properties that will favor the encapsulation of insulin. Each system was characterized in terms of their particle size distribution, morphology, zeta potential, and polydispersity index. In vitro release of insulin was evaluated in acidic solution (pH 1.2) and phosphate buffer solution (pH 7.4), and the hypoglycaemic activity was evaluated in diabetes rats. The prepared insulin-loaded NPs displayed particles with relatively smooth surfaces and an average particle size of 479.6 and 504.1 nm for A1 and A2, respectively. Zeta potential and polydispersity index, ranged from 22.1 to 31.2 mV and 0.155-0.185, respectively. The encapsulating efficiency for the systems A1 and A2 were 88.6 and 92.5, respectively, and a self-sustained release of encapsulated insulin was observed for over a period of 8 h. In vivo studies revealed a pronounced hypoglycaemic effect in diabetic rats after peroral administration of the insulin-loaded NPs compared to the effect caused by free oral insulin solution. In addition, both the pharmacokinetic and toxicity results showed low plasma clearance of insulin and no signs of toxicity on the liver enzyme and cell viability, which suggested good biocompatibility of the NPs formulations. Overall, the formation of NPs of insulin with chitosan and snail mucin represents a potentially safe and promising approach to protect insulin and enhance its peroral delivery.

A new lipid-based oral delivery system of erythromycin for prolong sustain release activity.

Erythromycin-loaded solid lipid microparticles (SLM) based on solidified reverse micellar solution (SRMS) as an oral delivery formulation was studied. Hot homogenization technique was employed to prepare erythromycin stearate-loaded SLMs using blends of Softisan® 154 and Phospholipon® 90H or beeswax in the ratio of 1:2, and characterized in vitro. Antibacterial evaluation of the formulations was carried out by agar diffusion technique against some selected clinical isolates of bacterial. Preliminary pharmacokinetic study was performed after oral administration in male Albino rats. The results of matrix contain Softisan® 154 and phospholipon® 90H (1:2) showed that erythromycin-loaded SLM was smooth; particle size ranged from 10.3 ±â€¯11.24 µm to 18.1 ±â€¯10.11 µm and maximum encapsulation efficiency and loading capacity were 95.11 ±â€¯0.3% and 43.22 ±â€¯0.1 mg, respectively. While that of beeswax- containing matrix showed maximum particle size of 18.9 ±â€¯21.10 µm, maximum encapsulation efficiency of 89.01 ±â€¯0.11% and loading capacity of 39.02 ±â€¯0.12 mg. All the formulations had prolonged release and antibacterial activity. Significantly (p > 0.05), prolonged plasma erythromycin concentration was obtained in the optimized formulation (>14 h) compared with commercial sample of erythromycin tablet (10h). Erythromycin stearate-loaded SLMs formulation could serve as an alternative to conventional oral formulation of erythromycin.

Surface-modified mucoadhesive microgels as a controlled release system for miconazole nitrate to improve localized treatment of vulvovaginal candidiasis.

The use of conventional vaginal formulations of miconazole nitrate (MN) in the treatment of deep-seated VVC (vulvovaginal candidiasis) is limited by poor penetration capacity and low solubility of MN, short residence time and irritation at the application site. Surface-modified mucoadhesive microgels were developed to minimize local irritation, enhance penetration capacity and solubility and prolong localized vaginal delivery of MN for effective treatment of deep-seated VVC. Solid lipid microparticles (SLMs) were prepared from matrices consisting of hydrogenated palm oil (Softisan® 154, SF) and super-refined sunseed oil (SO) with or without polyethylene glycol (PEG)-4000, characterized for physicochemical performance and used to prepare mucoadhesive microgels (MMs) encapsulating MN, employing Polycarbophil as bioadhesive polymer. The MMs were evaluated for physicochemical performance and in vitro drug release in simulated vaginal fluid (pH=4.2), whereas mucoadhesive, rheological and stability tests, anticandidal efficacy in immunosuppressed estrogen-dependent female rats and vaginal tolerance test in rabbits were performed with optimized formulation. The amorphicity of 1:9 phytolipid blend (SO:SF) was increased in the presence of PEG-4000. The physicochemical properties of the SLMs and MMs indicated their suitability for vaginal drug delivery. Overall, MN-loaded PEGylated MMs exhibited significantly (p<0.05) more prolonged drug release than non-PEGylated MMs. Additionally, optimized PEGylated MMs was stable at 40±2°C over a period of 6months, viscoelastic, mucoadhesive, non-sensitizing, histopathologically safe and gave remarkably (p<0.05) higher reduction in Candida albicans load (86.06%) than Daktarin® (75.0%) and MN-loaded polymeric-hydrogel (47.74%) in treated rats in 12days. Thus, PEGylated MMs is promising for effective and convenient treatment of VVC.

Improved dissolution and anti-inflammatory activity of ibuprofen-polyethylene glycol 8000 solid dispersion systems.

BACKGROUND: The purpose of this study was to develop ibuprofen (IB)-polyethylene glycol (PEG) 8000 solid dispersions (SDs) and investigate them for in vitro dissolution and in vivo anti-inflammatory activity. MATERIALS AND METHODS: IB-PEG 8000 SDs were prepared by fusion method using varying combination ratios of IB and PEG 8000. Characterization based on surface morphology, particle size, absolute drug content, and Fourier transform infrared (FT-IR) spectroscopy was carried out on the SDs. The in vitro release of IB from the SDs was performed in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.4) without enzymes, whereas the anti-inflammatory activity was evaluated using egg albumin-induced rat paw edema model. RESULTS: Greenish brown, discrete, and irregularly shaped SDs of mean particle size range 113.5 ± 2.5-252.5 ± 1.9 µm, which were stable over 3 months, were obtained. The drug content of the SDs ranged from 73.4 ± 2.9 % to 83.5 ± 2.7%. Although the drug content increased with increased concentration of PEG 8000 in the SDs, the mean particle size decreased with increased concentration of PEG 8000 in the SDs. The FT-IR results indicate no strong chemical interaction of IB and PEG 8000 in the SDs. There was marked increase in the dissolution rate of IB from the SDs (P < 0.05) as compared to pure IB and physical mixture. The dissolution was better in SIF than in SGF. The increased dissolution rate of IB may be due to the formation of microcrystals, increased wettability and dispersibility in PEG 8000. The SDs showed good anti-inflammatory properties achieving up to 90% edema inhibition at 6 h while the pure sample of IB had 77% edema inhibition at 6 h. CONCLUSION: SDs based on IB-PEG 8000 is a good approach to enhance the dissolution rate and anti-inflammatory activity of IB, thus, encouraging further development of the SDs.

Formulation, characterization and evaluation of the effect of polymer concentration on the release behavior of insulin-loaded Eudragit(®)-entrapped mucoadhesive microspheres.

INTRODUCTION: The aim of this study was to use Eudragit(®) RL 100 (pH-independent polymer) and magnesium stearate (a hydrophobic droplet stabilizer) in combination to improve the controlled release effect of insulin-loaded Eudragit(®) entrapped microspheres prepared by the emulsification-coacervation technique. MATERIALS AND METHODS: Mucoadhesive insulin-loaded microspheres containing magnesium stearate and varying proportions of Eudragit(®) RL 100 were prepared by the emulsification-coacervation technique and evaluated for thermal properties, physicochemical performance, and in vitro dissolution in acidic and subsequently basic media. RESULTS: Stable, spherical, brownish, discrete, free-flowing and mucoadhesive insulin-loaded microspheres with size range of 14.20 ± 0.30-19.80 ± 0.60 µm and loading efficiency of 74.55 ± 1.05-75.90 ± 1.94% were formed. After 3 h, microspheres prepared with insulin: Eudragit(®) RL 100 ratios of 1:4, 1:6, and 1:8 released 73.40 ± 1.38, 66.20 ± 1.59, and 71.30 ± 1.27 (%) of insulin, respectively. CONCLUSION: The physicochemical and physico-technical properties of the microspheres developed in this study demonstrated the effectiveness of the Eudragit(®) RL entrapped mucoadhesive microspheres (prepared by the emulsification-coacervation technique using varying polymer concentration) as a carrier system for oral insulin delivery.

Investigation of novel solid lipid microparticles based on homolipids from Bos indicus for the delivery of gentamicin.

BACKGROUND: The aim of this study was to formulate solidified reverse micellar solution (SRMS)-based solid lipid microparticles (SLMs) using homolipids from tallow fat (Bos indicus) and evaluate its potential for enhanced delivery of gentamicin. MATERIALS AND METHODS: SLMs were formulated by melt-emulsification using SRMS (15% w/w Phospholipon(®) 90G in 35% w/w Bos indicus), polyethylene glycol 4000 (PEG) and gentamicin (1.0, 2.0, 3.0% w/w), and characterized with respect to size, morphology, encapsulation efficiency % and pH-dependent stability. The in vitro release of gentamicin from the SLMs was performed in phosphate buffer (pH 7.4) while bioevaluation was carried out using clinical isolates of Staphylococcus aureus and Escherichia coli. RESULTS: Results showed that the lipid matrix accommodated gentamicin in a concentration-dependent manner, and that stable and spherical SLMs with size range of 18.62 ± 1.24-20.59 ± 1.36 µm and 21.35 ± 1.57-50.62 ± 2.37 µm respectively for unloaded and drug-loaded formulations were obtained. The in vitro drug release studies revealed that SRMS-based SLMs could better be used to control the release of gentamicin than gentamicin injection. Results of sensitivity test revealed that the SLMs time-dependently and capacity-limitedly produced greater inhibition zone diameters (IZDs) than the standards, an indication of improved bioactivity against the test organisms, with greater IZDs against S. aureus than E. coli. Overall, SLMs containing 2% w/w SRMS, 3% w/w gentamicin and PEG 4000 entrapped the highest amount of drug, achieved complete drug release and gave highest IZD against the organisms within 420 min, while plain gentamicin gave the least. CONCLUSION: This research has shown that SLMs based on Bos indicus and P90G is a potential carrier system for dissolution and bioactivity enhancement of gentamicin.

Formulation, in vitro and in vivo evaluation of halofantrine-loaded solid lipid microparticles.

CONTEXT: Formulation, characterization, in vitro and in vivo evaluation of halofantrine-loaded solid lipid microparticles (SLMs). OBJECTIVE: The objective of the study was to formulate and evaluate halofantrine-loaded SLMs. MATERIALS AND METHODS: Formulations of halofantrine-loaded SLMs were prepared by hot homogenization and thereafter lyophilized and characterized using particle size, pH stability, loading capacity (LC) and encapsulation efficiency (EE). In vitro release of halofantrine (Hf) from the optimized SLMs was performed in SIF and SGF. In vivo study using Peter's Four day suppressive protocol in mice and the mice thereafter subjected to histological studies in kidney and liver. RESULTS: Results obtained indicated that EE of 76.32% and 61.43% were obtained for the SLMs containing 7% and 3% of Hf respectively. The SLMs loaded with 3% of Hf had the highest yield of 73.33%. Time-dependent pH stability analysis showed little variations in pH ranging from 3.49 ± 0.04 to 4.03 ± 0.05. DISCUSSION: The SLMs showed pH-dependent release profile; in SIF (43.5% of the drug for each of H2 and H3) compared with SGF (13 and 18% for H2 and H3 respectively) after 8 h. The optimized SLMs formulation and Halfan® produced a percentage reduction in parasitemia of 72.96% and 85.71% respectively. The histological studies revealed that the SLMs formulations have no harmful effects on the kidney and liver. CONCLUSION: SLMs formulations might be an alternative for patients with parasitemia as there were no harmful effects on vital organs of the mice.

Influence of magnesium stearate on the physicochemical and pharmacodynamic characteristics of insulin-loaded Eudragit entrapped mucoadhesive microspheres.

Effective oral insulin delivery has remained a challenge to the pharmaceutical industry. This study was designed to evaluate the effect of magnesium stearate on the properties of insulin-loaded Eudragit® RL 100 entrapped mucoadhesive microspheres. Microspheres containing Eudragit® RL 100, insulin, and varying concentrations of magnesium stearate (agglomeration-preventing agent) were prepared by emulsification-coacervation method and characterized with respect to differential scanning calorimetry (DSC), morphology, particle size, loading efficiency, mucoadhesive and micromeritics properties. The in vitro release of insulin from the microspheres was performed in simulated intestinal fluid (SIF, pH 7.2) while the in vivo hypoglycemic effect was investigated by monitoring the plasma glucose level of the alloxan-induced diabetic rats after oral administration. Stable, spherical, brownish, mucoadhesive, discrete and free flowing insulin-loaded microspheres were formed. While the average particle size and mucoadhesiveness of the microspheres increased with an increase in the proportion of magnesium stearate, loading efficiency generally decreased. After 12 h, microspheres prepared with Eudragit® RL 100: magnesium stearate ratios of 15:1, 15:2, 15:3 and 15:4 released 68.20 ± 1.57, 79.40 ± 1.52, 76.60 ± 1.93 and 70.00 ± 1.00 (%) of insulin, respectively. Reduction in the blood glucose level for the subcutaneously (sc) administered insulin was significantly (p ≤ 0.05) higher than for most of the formulations. However, the blood glucose reduction effect produced by the orally administered insulin-loaded microspheres prepared with four parts of magnesium stearate and fifteen parts of Eudragit® RL 100 after 12 h was equal to that produced by subcutaneously administered insulin solution. The results of this study can suggest that this carrier system could be an alternative for the delivery of insulin.

Design of novel miconazole nitrate transdermal films based on Eudragit RS100 and HPMC hybrids: preparation, physical characterization, in vitro and ex vivo studies.

The objective of this study was to formulate and evaluate transdermal films containing miconazole nitrate (MN), a poorly water-soluble imidazole antifungal agent, with a view to enhancing its delivery across intact skin. Transdermal films of MN were formulated by solvent casting technique using admixtures of film-forming polymers - Eudragit RS100 and hydroxypropylmethylcellulose (HPMC) (2:8, 4:6, 5:5, 6:4 and 8:2) with polyethylene glycol 8000 (plasticizer and permeation enhancer) and Tween 80 (mobile surfactant). The films were evaluated for weight uniformity, folding endurance, thickness, moisture loss and uptake, bioadhesive strength, drug content, skin irritation on rabbits and time-resolved stability. The ex vivo release of MN from the films was carried out using a modified Franz diffusion apparatus while the microbiological evaluation was conducted using a clinical isolate of Candida albicans. Overall results indicate that films made with two portions of Eudragit RS100 and eight portions of HPMC (batch T-1) had the least weight variation (57.33 ± 0.27 mg), folding endurance (307.90 ± 4.17), moisture uptake (1.37 ± 0.28%) and thickness (145.9 ± 2.08 µm), but highest drug content (97.50 ± 2.43%) and bioadhesive strength (81.40 ± 2.03 dyne/cm2), best bioactivity and in vitro skin permeation through rat skin with highest permeation flux (5.161 µg/cm2 h) and permeation coefficient (1.032 × 10-6 cm/h) compared to all other formulations. This study has established that transdermal films based on 2:8 admixtures of Eudragit RS100 and HPMC could offer a promising approach for the treatment of skin infections caused by MN-susceptible fungi.

Solid lipid micro-dispersions (SLMs) based on PEGylated solidified reverse micellar solutions (SRMS): a novel carrier system for gentamicin.

The purpose of this study was to formulate and evaluate novel PEGylated solidified reverse micellar solutions (SRMS)-based solid lipid microparticles (SLMs) for improved delivery of gentamicin. Lipid matrix (SRMS) [consisting of 15% w/w Phospholipon® 90G (P90G) in 35% w/w dika wax (Irvingia gabonensis) was formulated and characterized by differential scanning calorimetry (DSC). SLMs were formulated by melt-emulsification using the SRMS, PEG 4000 and gentamicin (1.0, 2.0, 3.0% w/w), and their physicochemical as well as pharmacokinetic parameters determined. In vitro permeation of gentamicin from the SLMs through artificial membrane (0.22 µm pore size) was carried out using Franz's cell and phosphate-buffered saline (PBS, pH 7.4) as acceptor medium, while bioevaluation was performed using clinical isolates of Pseudomonas aeruginosa and Staphylococcus aureus. Stable and irregularly-shaped gentamicin-loaded SLMs of size range 34.49 ± 2.56 to 53.52 ± 3.09 µm were obtained. The SLMs showed sustained drug permeation and exhibited time-dependent and capacity-limited bioactivity. Overall, SLMs containing 2% w/w SRMS, 3% w/w gentamicin and PEG 4000 entrapped the highest amount of drug, gave highest IZD against the test organisms and highest permeation flux (5.239 µg/cm(2).min) and permeation coefficient (1.781 × 10(-6)cm/min) within 420 min, while pure gentamicin gave the least. Preliminary in vivo pharmacokinetic studies also showed an AUC-24 of 1507 µg/h/ml for the optimized formulation, while that of oral drug solution was 678 µg/h/ml. This showed a 2.2-fold increase in the systemic bioavailability of gentamicin from the optimized formulation. PEGylated SRMS-based SLMs prepared with heterolipid from Irvingia gabonensis would likely offer a reliable delivery system for gentamicin.

Formulation and characterization of hydrochlorothiazide solid lipid microparticles based on lipid matrices of Irvingia fat.

INTRODUCTION: The purpose of this study was to improve the solubilization, bioavailability, and permeability of hydrochlorothiazide (HCTZ) by the formulation and characterization of HCTZ solid lipid microparticles (SLMs) based on fat derived from Irvingia gabonensis var. excelsa (Irvingia wombolu) and Phospholipon(®)90G (P90G). MATERIALS AND METHODS: Irvingia fat was extracted from the nut of I. gabonensis var. excelsa using petroleum ether (40-60°C). HCTZ loaded SLM were formulated using hot homogenization method with 5% w/w Irvingia fat/P90G at each of 1:0, 9:1, 4:1, and 3:1 ratios, 1% w/w HCTZ, 1.5% w/w Labrasol(®) surfactant and distilled water. Subsequently, particle size analysis, pH, syringeability, drug encapsulation efficiency (EE%), yield, freeze-thaw cycle test, drug release, diffusion, and kinetics were evaluated. RESULTS: The SLM dispersions showed a particle size range of 10.15 ± 2.36 to 13.50 ± 6.88 µm and pH of 5.6-6.4 while dispersions containing 3:1 Irvingia fat/P90G passed through most of the needles (18G, 21G, and 22G) after syringeability studies. A single freeze-thaw cycle caused loss of physical integrity. The EE% of the SLMs were ≥80%, with high yield. The highest drug release and diffusion was observed with SLMs prepared with 3:1 Irvingia fat-P90G mixture (HDP3) and Higuchi model best described the kinetics of the HCTZ release by Fickian diffusion. CONCLUSION: The release and permeability of HCTZ was improved by its incorporation into Irvingia fat and P90G (3:1) as SLMs.

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.

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.

Pharmacodynamics of piroxicam from novel solid lipid microparticles formulated with homolipids from Bos indicus.

The dissolution of piroxicam is a limiting step in its bioavailability on account of its hydrophobicity. The objective of this research was to formulate novel solid lipid microparticles (SLMs) based on homolipids (admixtures of tallow fat (TF) and Softisan(®) 142 (SFT) templated with Phospholipon(®) 90G (P90G), a heterolipid for the delivery of piroxicam. Lipid matrices consisting of TF and SFT in ratios of 1:1, 1:2 and 2:1 were templated with the heterolipid, P90G and characterized by differential scanning calorimetry (DSC). The SLMs produced by hot homogenization technique using the matrices were characterized in terms of thermal properties, particle size, morphology, drug encapsulation efficiency, stability studies and in vitro diffusion studies. In vivo pharmacodynamic study was performed using egg albumin- induced pedal edema in rats. The results showed that addition of Softisan(®) 142 improved the drug holding capacity of the micellar solution of 2:1 mixture of TF and SFT. The in vitro diffusion of piroxicam from this SLM showed maximum release of 87.53 % and followed non-Fickian diffusion kinetic mechanism. At dose equivalence of 10 mg, piroxicamloaded SLMs showed superior in vivo anti-inflammatory properties at 3 h than Feldene(®) and the pure drug sample. This study has shown that surface-modified SLMs could confer favourable properties with respect to drug release and antiinflammatory activity on SLMs for the delivery of piroxicam, thus encouraging further development of the formulations.