<Emphasis Type="Italic">In Situ</Emphasis> Gelling Gelrite/Alginate Formulations as Vehicles for Ophthalmic Drug Delivery

The objective of this study was to develop an ion-activated in situ gelling vehicle for ophthalmic delivery of matrine. The rheological properties of polymer solutions, including Gelrite, alginate, and Gelrite/alginate solution, were evaluated. In addition, the effect of formulation characteristics on in vitro release and in vivo precorneal drug kinetic of matrine was investigated. It was found that the optimum concentration of Gelrite solution for the in situ gel-forming delivery systems was 0.3% (w/w) and that for alginate solution was 1.4% (w/w). The mixture of 0.2% Gelrite and 0.6% alginate solutions showed a significant enhancement in gel strength at physiological condition. On the basis of the in vitro results, the Gelrite formulations of matrine-containing alginate released the drug most slowly. For each tested polymer solution, the concentration of matrine in the precorneal area was higher than that of matrine-containing simulated tear fluid (STF) almost at each time point (p < 0.05). The area under the curve of formulation 16 (0.2%Gelrite/0.6%alginate) was 4.65 times greater than that of containing matrine STF. Both the in vitro release and in vivo pharmacological studies indicated that the Gelrite/alginate solution had the better ability to retain drug than the Gelrite or alginate solutions alone. The tested formulation was found to be almost non-irritant in the ocular irritancy test. The overall results of this study revealed that the Gelrite/alginate mixture can be used as an in situ gelling vehicle to enhance ocular retention.     

Preparation and <Emphasis Type="Italic">In Vitro</Emphasis>/<Emphasis Type="Italic">In Vivo</Emphasis> Evaluation of Microparticle Formulations Containing Meloxicam

In this study, we have formulated chitosan-coated sodium alginate microparticles containing meloxicam (MLX) and aimed to investigate the correlation between in vitro release and in vivo absorbed percentages of meloxicam. The microparticle formulations were prepared by orifice ionic gelation method with two different sodium alginate concentrations, as 1% and 2% (w/v), in order to provide different release rates. Additionally, an oral solution containing 15 mg of meloxicam was administered as the reference solution for evaluation of in vitro/in vivo correlation (ivivc). Following in vitro characterization, plasma levels of MLX and pharmacokinetic parameters [elimination half-life (t _1/2), maximum plasma concentration (C _max), time for C _max (t _max)] after oral administration to New Zealand rabbits were determined. Area under plasma concentration–time curve (AUC_0–∞) was calculated by using trapezoidal method. A linear regression was investigated between released% (in vitro) and absorbed% (in vivo) with a model-independent deconvolution approach. As a result, increase in sodium alginate content lengthened in vitro release time and in vivo t _max value. In addition, for ivivc, linear regression equations with r ² values of 0.8563 and 0.9402 were obtained for microparticles containing 1% and 2% (w/v) sodium alginate, respectively. Lower prediction error for 2% sodium alginate formulations (7.419 ± 4.068) compared to 1% sodium alginate formulations (9.458 ± 5.106) indicated a more precise ivivc for 2% sodium alginate formulation.     

Systematic Development of Transethosomal Gel System of Piroxicam: Formulation Optimization, <Emphasis Type="Italic">In Vitro</Emphasis> Evaluation,and <Emphasis Type="Italic">Ex Vivo</Emphasis> Assessment

Piroxicam is used in the treatment of rheumatoid arthritis, osteoarthritis, and other inflammatory diseases. Upon oral administration, it is reported to cause ulcerative colitis, gastrointestinal irritation, edema and peptic ulcer. Hence, an alternative delivery system has been designed in the form of transethosome. The present study describes the preparation, optimization, characterization, and ex vivo study of piroxicam-loaded transethosomal gel using the central composite design. On the basis of the prescreening study, the concentration of lipids and ethanol was kept in the range of 2–4% w/v and 0–40% v/v, respectively. Formulation was optimized by measuring drug retention in the skin, drug permeation, entrapment efficiency, and vesicle size. Optimized formulation was incorporated in hydrogel and compared with other analogous vesicular (liposomes, ethosomes, and transfersomes) gels for the aforementioned responses. Among the various lipids used, soya phosphatidylcholine (SPL 70) and ethanol in various percentages were found to affect drug retention in the skin, drug permeation, vesicle size, and entrapment efficiency. The optimized batch of transethosome has shown 392.730 μg cm^?2 drug retention in the skin, 44.312 μg cm^?2 h^?1 drug permeation, 68.434% entrapment efficiency, and 655.369 nm vesicle size, respectively. It was observed that the developed transethosomes were found superior in all the responses as compared to other vesicular formulations with improved stability and highest elasticity. Similar observations were noted with its gel formulation.     

Development and Characterization of Mucoadhesive <Emphasis Type="Italic">In Situ</Emphasis> Nasal Gel of Midazolam Prepared with <Emphasis Type="Italic">Ficus carica</Emphasis> Mucilage

The objective of the present study was to prepare mucoadhesive in situ nasal gels with mucilage isolated from fig fruits (Ficus carica, family: Moraceae) containing midazolam hydrochloride. Nasal gels of midazolam were prepared using three different concentrations (0.5%, 1.0% and 1.5% w/v) of F. carica mucilage (FCM) and synthetic polymers (hydroxypropylmethyl cellulose and Carbopol 934). Evaluation of FCM showed that it was as safe as the synthetic polymers for nasal administration. In situ gels were prepared with mixture Pluronic F127 and mucoadhesive agents. Evaluation of the prepared gels was carried out, including determination of viscosity, texture profile analysis and mucoadhesive strength. In vitro drug permeation study was conducted with the gels prepared with and without permeation enhancer (0.5% w/v sodium taurocholate) using excised goat nasal mucosa. In vitro permeation profiles were evaluated, and histological study of nasal mucosae before and after permeation study was also conducted to determine histological change, if any. In vivo experiments conducted in rabbits further confirmed that in situ nasal gels provided better bioavailability of midazolam than the gels prepared from synthetic mucoadhesive polymers. It was observed that the nasal gel containing 0.5% FCM and 0.5% sodium taurocholate exhibited appropriate rheological, mechanical and mucoadhesive properties and showed better drug release profiles. Moreover, this formulation produced no damage to the nasal mucosa that was used for the permeation study, and absolute bioavailability was also higher compared to gels prepared from synthetic polymers.     

Development of Microemulsions and Microemulgels for Enhancing Transdermal Delivery of <Emphasis Type="Italic">Kaempferia parviflora</Emphasis> Extract

The purpose of this research was to develop microemulsions (ME) and microemulgels (MG) for enhancing transdermal delivery of Kaempferia parviflora (KP) extract. The methoxyflavones were used as markers. Various formulations of ME and MG containing 10% w/v KP extract were prepared, and the in vitro skin permeation and deposition were investigated. The potential ME system containing oleic acid (5% w/v), Tween 20 (20% w/v), PG (40% w/v), and water (35% w/v) was successfully formulated. ME with 10% w/v limonene (ME-L10%) showed higher methoxyflavones flux than ME-L5%, ME-L1%, ME without limonene, and KP extract in water, respectively. ME-L10% was selected for adding a gelling agent to form microemulgels (MG-L10%). However, the high viscosity of the gel formulation might control the diffusion of the compound from gel layer into the skin. Therefore, the liquid formulation provided potential ME droplets to deliver KP extract through the skin. Limonene also plays an effective role on the skin permeation, in which the histological image of the skin treated with ME-L10% exhibited larger space of each flattened keratinocyte layer in the stratum corneum compared to the skin treated with KP extract in water. Moreover, ME-L10% showed good stability. Therefore, ME-L10% was a potential formulation for improving transdermal delivery of KP extract.     

Improved Skin Penetration Using <Emphasis Type="Italic">In Situ</Emphasis> Nanoparticulate Diclofenac Diethylamine in Hydrogel Systems: <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Studies

Delivering diclofenac diethylamine transdermally by means of a hydrogel is an approach to reduce or avoid systemic toxicity of the drug while providing local action for a prolonged period. In the present investigation, a process was developed to produce nanosize particles (about 10 nm) of diclofenac diethylamine in situ during the development of hydrogel, using simple mixing technique. Hydrogel was developed with polyvinyl alcohol (PVA) (5.8% w/w) and carbopol 71G (1.5% w/w). The formulations were evaluated on the basis of field emission scanning electron microscopy, texture analysis, and the assessment of various physiochemical properties. Viscosity (163–165 cps for hydrogel containing microsize drug particles and 171–173 cps for hydrogel containing nanosize drug particles, respectively) and swelling index (varied between 0.62 and 0.68) data favor the hydrogels for satisfactory topical applications. The measured hardness of the different hydrogels was uniform indicating a uniform spreadability. Data of in vitro skin (cadaver) permeation for 10 h showed that the enhancement ratios of the flux of the formulation containing nanosize drug (without the permeation enhancer) were 9.72 and 1.30 compared to the formulation containing microsized drug and the marketed formulations, respectively. In vivo plasma level of the drug increased predominantly for the hydrogel containing nanosize drug-clusters. The study depicts a simple technique for preparing hydrogel containing nanosize diclofenac diethylamine particles in situ, which can be commercially viable. The study also shows the advantage of the experimental transdermal hydrogel with nanosize drug particles over the hydrogel with microsize drug particles.     

<Emphasis Type="Italic">In vitro</Emphasis> germplasm conservation of <Emphasis Type="Italic">Podophyllum peltatum</Emphasis> L. under slow growth conditions

Germplasm conservation of Podophyllum peltatum L. was attempted by using synthetic seed technology and media supplemented with osmotic agents. Excised buds from in vitro cultures were encapsulated in calcium alginate beads and cultured on different substrates then stored at 5, 10, and 25°C for up to 8 mo. Survival and vigor in re-growth were the parameters used to evaluate the germplasm storage conditions. Vigor in re-growth was measured by number of buds induced after storage, which was achieved on a substrate containing water solidified with 1% w/v agar under 10°C. In vitro storage of shoot cultures was also evaluated by supplementing osmotic agents, mannitol, or sorbitol to the media. Such treatment had a negative impact on post-storage re-growth (at 25°C), even though the inclusion of 2% w/v sorbitol and mannitol each to the media increased plantlet survival during 10°C storage treatment. A deleterious effect was noticed among cultures in re-growth when higher concentrations of these supplements were added to the media. Genetic stability was assessed following 8 mo of storage using a PCR-based multilocus DNA fingerprinting technique, amplified fragment-length polymorphism. No differences in the DNA fragment patterns were observed using eight primer combinations in stored clones. However, a polymorphic band was noticed in the accession that served as explant source, suggesting that the mutation has occurred prior to this study perhaps during the 9 years of in vitro cultivation.     

<Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Evaluation of Proniosomes Containing Celecoxib for Oral Administration

The objectives of this research were to prepare celecoxib proniosomes and evaluate the influence of proniosomal formulation on the oral bioavailability of the drug in human volunteers. A new proniosomal delivery system for a poorly water-soluble drug such as celecoxib was developed and subjected to in vitro and in vivo studies. Proniosomes were prepared by sequential spraying method, which consisted of cholesterol, span 60, and dicetyl phosphate in a molar ratio of 1:1: 0.1, respectively. The average entrapment percent of celecoxib proniosome-derived niosomes was about 95%. The prepared proniosomes showed marked enhancement in the dissolution of celecoxib as compared to pure drug powder. The bioavailability of 200 mg single dose of both celecoxib proniosomal formulation and a conventional marketed celecoxib capsule was studied in human volunteers. The obtained results show that the proniosomal formulation significantly improved the extent of celecoxib absorption than conventional capsule. The mean relative bioavailability of the proniosomal formulation to the conventional capsule was 172.06 ± 0.14%. The mean T _max for celecoxib was prolonged when given as proniosomal capsule. There was no significant difference between the values of K _el and t _1/2 for both celecoxib preparations. In conclusion, the proniosomal oral delivery system of celecoxib with improved bioavailability was established.     

Naproxen Microparticulate Systems Prepared Using <Emphasis Type="Italic">In Situ</Emphasis> Crystallisation and Freeze-Drying Techniques

Poor drug solubility and dissolution rate remain to be one of the major problems facing pharmaceutical scientists, with approximately 40% of drugs in the industry categorised as practically insoluble or poorly water soluble. This in turn can lead to serious delivery challenges and poor bioavailability. The aim of this research was to investigate the effects of the surfactants, poloxamer 407 (P407) and caprol® PGE 860 (CAP), at various concentrations (0.1, 0.5, 1 and 3% w/v) on the enhancement of the dissolution properties of poorly water-soluble drug, naproxen, using in situ micronisation by solvent change method and freeze-drying. The extent at which freeze-drying influences the dissolution rate of naproxen microcrystals is investigated in this study by comparison with desiccant-drying. All formulations were evaluated and characterised using particle size analysis and morphology, in vitro dissolution studies, differential scanning calorimetry (DSC), and Fourier transform infra-red (FT-IR) spectroscopy. An increase in poloxamer 407 concentration in freeze-dried formulations led to enhancement of drug dissolution compared to desiccator-dried formulations, naproxen/caprol® PGE 860 formulations and untreated drug. DSC and FT-IR results show no significant chemical interactions between drug and poloxamer 407, with only very small changes to drug crystallinity. On the other hand, caprol® PGE 860 showed some interactions with drug components, alterations to the crystal lattice of naproxen, and poor dissolution profiles using both drying methods, making it a poor choice of excipient.     

Optimization of <Emphasis Type="Italic">Renealmia mexicana</Emphasis> (Klotzsch ex. Petersen) cultivation <Emphasis Type="Italic">in vitro</Emphasis>

Renealmia mexicana (Klotzsch ex. Petersen) is a tropical plant found in southern México with an ornamental value and a potential source of curcuminoids. Its distribution in Chiapas has decreased because of deforestation and low propagation and germination rate, so a protocol for in vitro propagation was developed. An orthogonal experimental design of L₉ (3⁴) in triplicate was used to investigate the effect of 6-benzyl adenine (BA), indole butyric acid (IBA), silver nitrate (AgNO₃), and sucrose on shoot, root, and leaf development of plantlets grown in vitro. Plantlets with well-developed shoots and roots were transferred to pots containing a mixture of peat moss and agrolite for hardening before transfer to soil. The Murashige and Skoog (Physiol. Plant. 15:473–497, 1962) mineral medium (MS) supplemented with 4.4 μM BA, 2.5 μM IBA, 11.7 μM AgNO_3y and 5.5% (w/v) sucrose gave most shoots, 8.9 μM BA, 2.5 μM IBA, 17.7 μM AgNO₃ and 5.5% (w/v) sucrose most roots, and 8.9 μM BA, 4.9 μM IBA, 11.7 μM AgNO₃ and 3.0% (w/v) sucrose most leaves, although other combinations were statistically equivalent in each case. Sucrose was the factor that most explained the variation in the promotion of shoots, roots, and leaves. The protocol developed resulted in up to 100% survival when plantlets were transferred to soil using AgNO₃, confirming that hardening of plantlets in vitro using hormonal stimulation was a suitable strategy to improve acclimatization.     

<Emphasis Type="Italic">In vitro</Emphasis> flowering of <Emphasis Type="Italic">Perilla frutescens</Emphasis>

This study investigated the factors affecting in vitro flowering of Perilla frutescens. The shoots regenerated from cotyledonary and hypocotyl explants cultured on Murashige and Skoog (MS) medium supplemented with benzyladenine (BA) and indole-3-acetic acid, each at 0.5 mg l⁻¹, were excised and transferred to MS medium containing 30 g l⁻¹ of sucrose, 8.25 g l⁻¹ of ammonium nitrate, and 1.0 mg l⁻¹ of BA. After 40 d of culture, 86.2% of shoots flowered and most of which self-fertilized in vitro and produced mature fruits with viable seeds. These seeds were germinated and plants were grown to maturity and flowered in soil under greenhouse conditions. The in vitro flowering system reported in this study may facilitate rapid breeding of P. frutescens and offers a model system for studying the physiological mechanism of flowering.     

Attenuation of fibrosis <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis> with <Emphasis Type="Italic">SPARC</Emphasis> siRNA

Introduction  

SPARC is a matricellular protein, which, along with other extracellular matrix components including collagens, is commonly over-expressed in fibrotic diseases. The purpose of this study was to examine whether inhibition of SPARC can regulate collagen expression in vitro and in vivo, and subsequently attenuate fibrotic stimulation by bleomycin in mouse skin and lungs.     

<Emphasis Type="Italic">In vitro</Emphasis> culture studies on <Emphasis Type="Italic">Stevia rebaudiana</Emphasis>

Summary Shoot apex, nodal, and leaf explants of Stevia rebaudiana Bertoni can regenerate shoots when cultured on Murashige and Skoog (MS) medium supplemented with 6-benzyladenine (BA; 8.87 μM) and indole-3-acetic acid (5.71 μM). Rooting of the in vitro-derived shoots could be achieved following subculture onto auxin-containing medium. A survival rate of 70% was recorded at the hardening phase on the substrate cocopeat. The presence of the sweet diterpene glycosides, viz. stevioside and rebaudioside, was confirmed in the in vitro-derived tissues of Stevia using HPTLC techniques. Callus cultured on agar-solidified MS medium supplemented with BA (8.87 μM) and indole-3-butyric acid (9.80 μM) showed the highest sweetener content.     

Development and <Emphasis Type="Italic">In Vitro</Emphasis>/<Emphasis Type="Italic">In Vivo</Emphasis> Evaluation of Etodolac Controlled Porosity Osmotic Pump Tablets

The aim of the current work was the design and evaluation of etodolac controlled porosity osmotic pump (CPOP) tablets exhibiting zero-order release kinetics. Variables influencing the design of (1) core tablets viz., (a) osmogent type (sodium chloride, potassium chloride, mannitol, and fructose) and (b) drug/osmogent ratio (1:0.25, 1:0.50, and 1:0.75), and (2) CPOP tablets viz., (a) coating solution composition, (b) weight gain percentage (1–5%, w/w), and (c) pore former concentration (5%, 10%, and 20%, v/v), were investigated. Statistical analysis and kinetic modeling of drug release data were estimated. Fructose-containing core tablets showed significantly (P < 0.05) more retarded drug release rates. An inverse correlation was observed between drug/fructose ratio and drug release rate. Coating of the optimum core tablets (F4) with a mixture of cellulose acetate solution (3%, w/v), diethyl phthalate, and polyethylene glycol 400 (85:10:5, v/v, respectively) till a 4% w/w weight gain enabled zero-order sustained drug delivery over 24 h. Scanning electron microscopy micrographs of coating membrane confirmed pore formation upon contact with dissolution medium. When compared to the commercial immediate-release Napilac® capsules, the optimum CPOP tablets (F4–34) provided enhanced bioavailability and extended duration of effective etodolac plasma concentration with minimum expected potential for side effects in healthy volunteers.KEY WORDS: cellulose acetate, controlled porosity osmotic pump, etodolac, osmogent, zero order     

<Emphasis Type="Italic">In vitro</Emphasis> propagation of <Emphasis Type="Italic">Chimonanthus praecox</Emphasis> (L.), a winter flowering ornamental shrub

A procedure for the micropropagation of Chimonanthus praecox (L) Link, wintersweet, has been developed using buds from adult trees excised in spring. Shoot cultures established on Murashige and Skoog (1962) medium supplemented with 0.5 mg l⁻¹ 6-benzyladenine (BAP) and 0.1 mg l⁻¹ indole-3-butyric acid (IBA) were difficult to maintain in vitro through extended periods of time due to browning of the medium, shoot and leaf necrosis, and hyperhydricity. A treatment combining the use of 0.1% w/v activated charcoal and addition of a double phase agar-solidified/liquid medium improved propagation, enabling a successful in vitro propagation scheme to be developed. Optimal shoot multiplication occurred on medium containing 0.5 mg l⁻¹ BAP, and rooting on medium with 2.0 mg l⁻¹ IBA for 7 d, followed by transfer to hormone-free medium. Rooted plantlets were easily acclimated in a glasshouse and replanted and cultured outdoors.     

<Emphasis Type="Italic">In vitro</Emphasis> regeneration of medicinal plant <Emphasis Type="Italic">Centella asiatica</Emphasis>

This paper describes multiple shoot regeneration from leaf and nodal segments of a medicinally important herb Centella asiatica L. on Murashige and Skoog’s (MS) medium supplemented with a range of growth regulators. The highest number of multiple shoots was observed on MS augmented with 3.0 mg dm⁻³ N⁶-benzylaminopurine (BAP) and 0.05 mg dm⁻³ α-naphthaleneacetic acid (NAA). Leaf explant showed maximum percentage of cultures regenerating shoots (81.6 %), with the highest shoot number (8.3 shoots per explant) and the shoot length (2.1 cm) whereas, nodal explant showed less number of shoots with callus formation at the base cut end. Successive shoot cultures were established by repeatedly sub-culturing the original explant on a fresh medium. Rooting of in vitro raised shoots was best induced on half strength MS supplemented with 0.5 mg dm⁻³ indole-3-butyric acid (IBA) with highest percentage of shoot regenerating roots (76.8 %) with 3–4 roots per shoot. Plantlets were acclimated in Vermi-compost and eventually established in soil. Contents of chlorophyll, total sugars, reducing sugars and proteins were estimated in leaf tissue from both in vivo and in vitro raised plants. Chlorophyll content was higher in in vivo plants, whereas other three components were higher in in vitro plants.     

<Emphasis Type="Italic">In vitro</Emphasis> regeneration of <Emphasis Type="Italic">Leucaena leucocephala</Emphasis> by organogenesis and somatic embryogenesis

In the present study, in vitro regeneration system for a recalcitrant woody tree legume, Leucaena leucocephala (cvs. K-8, K-29, K-68 and K-850) from mature tree derived nodal explants as well as seedling derived cotyledonary node explants was developed. Best shoot initiation and elongation was found on full-strength Murashige and Skoog (MS) medium supplemented with 3 % (m/v) sucrose, 100 mg dm⁻³ myoinositol, 100 mg dm⁻³ glutamine, 20.9 μM N ⁶-benzylamino-purine (BAP) and 5.37 μM 1-naphthalene acetic acid (NAA). Rooting was induced in half-strength MS medium containing 2 % (m/v) sucrose, 100 mg dm⁻³ myoinositol, 14.76 μM indole-3-butyric acid (IBA) and 0.23 μM kinetin. The cultivar K-29 gave the best response under in vitro conditions. Rooted plantlets were subjected to hardening and successfully transferred to greenhouse. Further, somatic embryogenesis from nodal explants of cv. K-29 via an intermittent callus phase was also established. Pronounced callusing was observed on full-strength MS medium containing 3 % (m/v) sucrose, 100 mg dm⁻³ myoinositol, 40.28 μM NAA and 12.24 μM BAP. These calli were transferred to induction medium and maximum number of globular shaped somatic embryos was achieved in full-strength MS medium fortified with 3 % (m/v) sucrose, 100 mg dm⁻³ myoinositol, 15.0 μM 2,4-dichlorophenoxyacetic acid (2,4-D), 5.0 μM BAP and 1.0 mM proline. Moreover, an increase in endogenous proline content up to 28^th day of culture in induction medium was observed. These globular shaped somatic embryos matured in full-strength MS medium with 3 % (m/v) sucrose, 100 mg dm⁻³ myoinositol, 10.0 μM BAP, 2.5 to 5.0 μM IBA and 0.5 mM spermidine.     

Topical Delivery of Fenoprofen Calcium <Emphasis Type="Italic">via</Emphasis> Elastic Nano-vesicular Spanlastics: Optimization Using Experimental Design and <Emphasis Type="Italic">In Vivo</Emphasis> Evaluation

The aim of this study was to investigate the potential of surfactant-based nanovesicular system (spanlastics) for topical delivery of fenoprofen calcium (FPCa) to eliminate its oral gastrointestinal adverse effects. FPCa-loaded spanlastics were prepared by thin film hydration (TFH) technique according to a full factorial design to investigate the influence of formulation variables on the drug entrapment efficiency (%EE), particle size (PS), deformability index (DI), and the % drug released after 24 h through the cellulose membrane (Q24h) using Design-Expert® software. The optimized formula (composed of Span 60 and Tween 60 as an edge activator at weight ratio of 8: 2 in presence of Transcutol P as a cosolvent in the hydration media) exhibited the highest %EE (49.91 ± 2.60%), PS of 536.1 ± 17.14 nm, DI of 5.07 ± 0.06 g, and Q24h of 61.11 ± 2.70%; it was also characterized for morphology and physical stability. In vitro release study of FPCa-loaded spanlastic gel and conventional FPCa gel through a synthetic membrane and hairless rat skin were evaluated. The skin permeation study revealed that spanlastic gel exhibited both consistent and prolonged action. Finally, the % inhibition of carrageenan-induced rat paw edema of spanlastic gel was three times higher than the conventional FPCa gel after 24 h. In conclusion, spanlastic-based gel could be a great approach for improving topical delivery of fenoprofen calcium, providing both prolonged and enhanced anti-inflammatory activity in the treatment of arthritis.     

Dual-Drug Delivery System Based on <Emphasis Type="Italic">In Situ</Emphasis> Gel-Forming Nanosuspension of Forskolin to Enhance Antiglaucoma Efficacy

The present study was designed to improve the bioavailability of forskolin by the influence of precorneal residence time and dissolution characteristics. Nanosizing is an advanced approach to overcome the issue of poor aqueous solubility of active pharmaceutical ingredients. Forskolin nanocrystals have been successfully manufactured and stabilized by poloxamer 407. These nanocrystals have been characterized in terms of particle size by scanning electron microscopy and dynamic light scattering. By formulating Noveon AA-1 polycarbophil/poloxamer 407 platforms, at specific concentrations, it was possible to obtain a pH and thermoreversible gel with a pH_gel/T _gel close to eye pH/temperature. The addition of forskolin nanocrystals did not alter the gelation properties of Noveon AA-1 polycarbophil/poloxamer 407 and nanocrystal properties of forskolin. The formulation was stable over a period of 6 months at room temperature. In vitro release experiments indicated that the optimized platform was able to prolong and control forskolin release for more than 5 h. The in vivo studies on dexamethasone-induced glaucomatous rabbits indicated that the intraocular pressure lowering efficacy for nanosuspension/hydrogel systems was 31% and lasted for 12 h, which is significantly better than the effect of traditional eye suspension (18%, 4–6 h). Hence, our investigations successfully prove that the pH and thermoreversible polymeric in situ gel-forming nanosuspension with ability of controlled drug release exhibits a greater potential for glaucoma therapy.     

<Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Investigation of Drug-Eluting Implants for the Treatment of Periodontal Disease

This paper developed solvent-free drug-eluting implants for metronidazole delivery for the treatment of periodontal disease and investigated the characteristics of the drug’s release from the implants, both in vitro and in vivo, using an HPLC assay. The metronidazole exhibited a two-stage release behavior in vitro with an initial burst release followed by a diffusion-controlled release and then a secondary burst release. The accumulated drug release reached 100% on the 18th day, and the drug-eluting implant was totally dissolved on the same day. Additionally, the drug-eluting disks were implanted within the sub-gingival space of both lower incisors of six rabbits. The curve of in vivo drug release was smoother and showed a predominantly diffusion-controlled release. The implants were totally dissolved at 2 weeks after implantation. The concentration of metronidazole remained above the MIC₉₀ during the entire investigation.