Coacervation Phase Separation Method Research Articles

Fabrication of prostructured spanlastics gel for improving transdermal effect of dapagliflozin: In vitro characterization studies and in vivo antidiabetic activity

Dapagliflozin is a recently approved glucose-lowering agent for the management of type II diabetes mellitus. Low solubility and stability lead to its poor oral bioavailability. Prostructured spanlastic gel is very less hydrated preform of spanlastic vesicles. Therefore, the aim of this study was to explore the potential of prostructured spanlastic gel for enhancing both drug stability and transdermal delivery. The prostructured spanlastic gel formulations were fabricated by coacervation phase separation method, using Span 60 together with Tween 80 or Myrj 52 as an edge activator. Formulations were characterized for drug content, in vitro release and ex vivo skin permeability. Verification of vesicular form was assessed by hydration and the resultant formulations were characterized. Selected formulations were assessed for morphology, interaction of drug with other components, stability and antidiabetic activity. Drug content percentage of spanlastic gels was found to be in range 98.1±1.9 to 94.2±2.0%. Significant (p < 0.05) increase in drug release rate was observed when edge activator concentration was greater than 30%. Tween 80 containing formulations exhibited higher skin permeation than Myrj 52 containing ones at the same concentration of edge activator. Spanlastic vesicles were formed by hydration and had entrapment efficiency percentages ranging from 65.06±0.87% to 40.36±0.95%, mean vesicle sizes ranging from 136.1 nm to 56.52 nm and zeta potential values ranging from –29.7 mV to –6.94 mV. The morphologic examination verified formation of nanovesicular form. Thermal analysis and FT-IR confirmed encapsulation of drug inside spanlastic vesicles. Spanlastic gels showed higher stability and skin permeability when compared to vesicular form in hydroalcoholic gel. Spanlastic gels also showed prolonged hypoglycemic effect and blood glucose level reached below 135±4.7 mg/dL after 24h, when compared to hydroalcoholic gel (273±3 mg/dL) and oral suspension (271±5 mg/dL). In conclusion, spanlastic gel could be a promising carrier for enhancing transdermal delivery of dapagliflozin, offering both sustained and enhanced antidiabetic activity.

Development and in vitro characterization of the proliposome gel of terbinafine hydrochloride

The study was conducted to prepare the Proliposome Gel of Terbinafine Hydrochloride to improve the drug loading and to sustain the drug release of terbinafine hydrochloride. Proliposome gel of terbinafine hydrochloride were prepared by modified coacervation phase separation method by varying the concentrations of PC to cholesterol. The prepared proliposome gel was evaluated for its pH, viscosity, drug loading, and In vitro drug release studies. The appearance, particle size and drug entrapment of each produced formulation was also evaluated. All proliposome gel formulation made were consistent, homogenous, and white creamy gel.

Proniosomal gel mediated transdermal delivery of Donepezil HCl: Development and in vitro characterization

The aim of this research was to study the potential of proniosomal gel for transdermal delivery. Donepezil HCl loaded proniosomal gels were prepared by the coacervation phase separation method using different nonionic surfactants (spans and tweens). The prepared Donepezil HCl proniosomal gels were evaluated for various parameters such as particle size (PS), drug entrapment efficiency percentage (EE %), and in vitro drug release. Donepezil HCl loaded proniosomal gel was prepared successfully by coacervation phase separation method. The prepared proniosomal gel exhibited desired entrapment efficiency and Particle size. It was found that B2 which chosen as a best formula according to entrapment efficiency, Particle size, and in vitro release study. It was found that B2 which contains high concentration of span 60 is the most appropriate surfactant for the preparation of proniosomes. In vitro release studies proved that the prepared proniosomal gel contains Donepezil HCl considered to be a successful topical transdermal drug delivery system and provide a sustained release of encapsulated drug. Furthermore, there was no significant change in EE % and PS of Donepezil HCl proniosomal gel after storage for 6 months.

Formulation Development and Characterization of Acitretin Proniosomal gel: In-vivo Exploration against Imiquimod-induced Psoriasis in Experimental Animals

he main purpose of this study was to prepare and evaluate acitretin proniosomal gel (APG) and find out if the antipsoriatic formulation could prevent Imiquimod (IMQ) induced psoriasis in experimental animals. APG was developed and by coacervation phase separation method. Cholesterol and soya lecithin was used as membrane modifiers and tween 80 and span 60 as non-ionic surfactants. Characterization of the prepared proniosomal gel revealed that the optimized batch APG3 presented excellent formulation characteristics like the viscosity of 9710 ± 1.24 cps, rate of spontaneity as 13 ± 0.86, %entrapment efficiency of 94.91 ± 0.51, average hydrodynamic diameter of niosomes as 345.7 nm, polydispersibility index as 0.159 and ZP of -2.3 mV. In-vivo animal study of the optimized batch APG3 was performed along with biochemical estimations of oxidative parameters as glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase; also, TNF-α, IL-6 were estimated using ELISA sandwiched. Histopathological estimation along with psoriasis area severity index (PASI) scores in the IMQ-induced psoriatic model presented a significant fall in the scoring after treatment with APG3 compared with a psoriatic group. Primary dermal irritation scoring was also evaluated on Sprague Dawley rats. The results presented a considerable decline in skin irritation score compared with a psoriatic group. Also, the levels of GSH, SOD and catalase were increased in APG3 treated group as compared with a psoriatic group. While MDA level is decreased after topical treatment with APG3 compared with a psoriatic group. In conclusion, the optimized APG3 showed promising pharmacological effects in the treatment of psoriasis.

Design and Characterization of Calcipotriol Proniosomal Gel: In-vivo Exploration against Imiquimod-induced Psoriasis in Experimental Animals

The present work focuses on the preparation and evaluation of calcipotriol proniosomal gel (CPG) and find out if the antipsoriatic formulation could prevent imiquimod (IMQ) induced psoriasis in experimental animals. CPG was designed and developed by the coacervation phase separation method. Cholesterol and soya lecithin was used as membrane modifiers and tween 80 and span 60 as non-ionic surfactants. The developed proniosomal gels were characterized which revealed that the optimized batch CPG3 presented excellent formulation characteristics like viscosity of 9690 ± 1.43 cps, rate of spontaneity as 14 ± 1.37, %entrapment efficiency of 82.71 ± 0.48, the average hydrodynamic diameter of niosomes as 739.1 nm, polydispersibility index as 0.360 and ZP of -2.8 mV. In-vivo animal study of the optimized batch CPG3 was performed along with biochemical estimations of oxidative parameters such as glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase; also, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) were estimated using enzyme-linked immunoassay (ELISA) sandwiched. Histopathological estimation along with psoriasis area severity index (PASI) scores in the IMQ-induced psoriatic model revealed a significant decline in the scoring after treatment with CPG3 compared with a psoriatic group. Primary dermal irritation scoring was also evaluated on Sprague Dawley rats. The results revealed a considerable decrease in skin irritation score compared with a psoriatic group. Also, the levels of GSH, SOD and catalase were raised in CPG3 treated group as compared with a psoriatic group. While MDA level was declined after topical treatment with CPG3 compared with a psoriatic group. In conclusion, the optimized CPG3 showed promising pharmacological effects in the treatment of psoriasis

Formulation and Evaluation of Microcapsules of Aspirin by Coacervation Phase Separation Method

Microencapsulation is a process in which tiny particles or droplets are surrounded by a coating to give small capsules, with useful properties. Microcapsule is a small sphere with uniform wall around it. The material inside the microcapsule is referred to as the core, internal phase or fill, whereas the wall sometimes called as shell, coating or membrane. Microencapsulation is a rapidly expanding technology in which very tiny droplets or particles of liquid or solid material are surrounded or coated with a continuous film of polymeric material. Aspirin (Acetylsalicylic acid) is a Non steroidal anti-inflammatory drug. It inhibits platelets aggregation and prolong bleeding time. This research article will emphasize formulation and evaluation of microcapsules of aspirin by coacervation phase separation method. coacervation phase separation techanique have been widely used to incorporate drugs into polymeric microcapsules.

Spanlastics gel-A novel drug carrier for transdermal delivery of glimepiride

Glimepiride (3rd-generation sulfonylurea) is used for treatment of type 2 diabetes, but its oral administration has been associated with severe gastric disturbances such as nausea, vomiting, heartburn, anorexia, haemolytic anaemia. Accordingly, the transdermal route may represent a potentially suitable alternative. This work investigates the usefulness of a novel drug carrier system for transdermal application. The system investigated were called spanlastics gels and constituted span 60 with edge activator (tween 60 or tween 80). Spanlastics gel has been introduced as a stable form alternative to the liquid formulations of spanlastics. Spanlastics gels were prepared by coacervation phase separation method. Entrapment efficiency and size of spanlastics vesicles produced from the hydration of spanlastics gels were characterised. In vitro release and skin permeation of glimepiride from various spanlastics gel formulations were investigated across mixed cellulose membrane and excised rabbit skin. The obtained results indicated that the maximum entrapment efficiency was 65.36% when the tween 60 content was 30%. The drug release and permeation were increase as the concentration of edge activator increased. Spanlastics gel prepared with Tween 80 at concentration 50% showed higher permeability and flux value (248.69 µg/cm2and 8.31 µg/cm2.h, respectively) through rabbit skin.

Effect of Eudragit S 100 polymer on sustained release of sodium diclofenac coated and uncoated microspheres

Diclofenac sodium were taken as a model drug and belongs to NSAIDS. Diclofenac sodium prevents production of prostaglandins and thus exerts its analgesic action and inhibits leukocyte formation to induce anti-inflammatory action. It is tremendously recommended to reduce and overcome signs and symptoms of rheumatoid arthritis, osteo-arthritis andankylosing spondylitis. This present study was to investigate the dissolution profile and release kinetics of modified release diclofenac sodium microspheres containing sodium alginate and Eudragit S-100. Microspheres were prepared by using ionotropic gelation technique and coated by using coacervation phase separation method using different ratios of eudragit S100 which is a pH sensitive polymer. Both coated and uncoated diclofenac sodium microspheres were evaluated for % yield, entrapment efficiency, flow property, in vitro percent drug release. which were spherical in shape, were rough and smooth, respectively. The size of the core microspheres ranged from 450 to 550 μm and the size of the coated microspheres ranged from 500 to 700 μm. The core microspheres sustained the release for 12hrs in a pH progression medium mimicking the condition of GIT. The release studies of coated microspheres were performed in a similar dissolution medium as mentioned above. In acidic medium, the release rate was much slower. However, the drug was released quickly at pH 7.4 and their release was sustained up to 24 hrs. Finally, it was concluded that eudragit L100 and ethyl cellulose were appropriate polymers to prepare microspheres of diclofenac sodium as modified release drug delivery system.

Formulation of tizanidine hydrochloride–loaded provesicular system for improved oral delivery and therapeutic activity employing a 23 full factorial design

Tizanidine hydrochloride (TZN) is one of the most effective centrally acting skeletal muscle relaxants. The objective of this study is to prepare TZN-loaded proniosomes (TZN-PN) aiming at enhanced oral delivery and therapeutic activity. TZN-PN were prepared by coacervation phase separation method. The developed vesicles were characterized via entrapment efficiency percentage (EE%), vesicular size (VS), and zeta potential (ZP). A 23 full factorial design was employed to attain an optimized TZN-PN formulation. The optimized TZN-PN were further characterized via in vitro release study and transmission electron microscopy (TEM). In vivo rotarod test was employed for determination of the muscle relaxant activities of rats and levels of GABA and EAAT2 were detected. The developed TZN-PN exhibited relatively high EE% (75.78–85.45%), a VS ranging between (348–559 nm), and a ZP (−26.47 to −59.64). In vitro release profiles revealed sustained release of TZN from the optimized TZN-PN, compared to free drug up to 24 h. In vivo rotarod study revealed that the elevation in coordination was in the following order: normal control < free TZN < market product < TZN-PN (F6). Moreover, the optimized TZN-PN exhibited significant elevated coordination activity by 39% and 26% compared to control group and market product group, respectively. This was accompanied with an elevation in both GABA and EAAT2 serum levels. Thus, it could be concluded that encapsulation of TZN in the provesicular nanosystem proniosomes has enhanced the anti-nociceptive effect of the drug and consequently its therapeutic activity.Graphical abstract

Formulation and Characterization of Hydrogel of Proniosomes Loaded Diclofenac Sodium

Diclofenac Sodium is a non-steroidal anti-inflammatory drug (NSAID), which has analgesic, anti-inflammatory, and antipyretic effects. Diclofenac sodium topically (gel 1%) has mild site reactions, with a relatively short duration of action and low permeability need for multiple uses. This study aimed to produce hydrogel of proniosomes to enhancing solubility and permeation of diclofenac topical used. Proniosome was prepared by using the coacervation phase separation method using Span 60 and Tween 80, lecithin and cholesterol. The hydrogel base was prepared from carbopol 940, then Proniosome was mixed in ratio one to one (1:1). Viscosity, release, permeation and stability were assayed. Results revealed a successfully prepared hydrogel loaded with proniosomes, which was consequently loaded with its payload. The release study carried out in vitro revealed a control-released behaviour over 28 hours which was 6 fold higher than the ordinary preparation i.e. lack of proniosomes. To sum up, the hydrogel of Proniosome preparation loading with Diclofenac Sodium was approved to overcome controlled release and skin permeation problems.

Oral Bioavailability of Curcumin Enhanced Using Different Surfactant for Preparing Proniosomal Gel

Purpose: The aim of the present study was to enhance the oral bioavailability of curcumin using different surfactant and vehicle for preparing proniosomal gel. Methods: Curcumin comes under BCS Class IV which is having low solubility and low permeability and poor bioavailability. Buccal drug delivery can bypass such problems and leads to increase in bioavailability. Proniosomes offer excellent potential for improved drug delivery through versatile routes, by overcome the permeation barriers. Trial batches of proniosomal gel are prepared by coacervation phase separation method using different concentration of surfactant (Span 20, Span 40, Span 60, and Span 80) with cholesterol, soyalecithin, and vehicles such as 0.1% glycerol solution or pH 6.8. The formulated systems were characterized to find out the effects of surfactant on vesicle size, % entrapment efficiency, and % drug release and permeation at 6 h. Stability studies for proniosomal gel were carried out for 4 weeks. Results and Conclusion: It suggested that formulation (F2) containing Span 20 and phosphate buffer pH 6.8 has high entrapment efficiency, drug release, and permeation as compare to the other formulations and it can enhance the delivery of curcumin through oral route and can improve the bioavailability of drug.

Formulation and evaluation of proniosome loaded sertaconazole nitrate for topical application

Proniosomal technology is a novel solution for poorly soluble drugs. Proniosomes are water-soluble carrier particles which are coated with non-ionic surfactants. Proniosomal gels were prepared by coacervation phase separation method using non-ionic surfactants, lipid carriers and cholesterol as a membrane stabilizer. FTIR compatibility studies revealed that the drug and excipients were compatible. All formulations were evaluated for pH, drug content, extrudability, spreadability, viscosity, in-vitro, ex-vivo, skin irritation and stability studies. Among formulations prepared, F80H1 has shown higher % EE (83.02) and least diffusion through dialysis membrane i.e., 17.68%. With ex-vivo studies, F80H1 formulation has shown highest skin deposition and lower flux of sertaconazole nitrate through the rat skin. F80H1 was selected as final optimized formulation. F80H1 exhibited good stability and SEM studies revealed that the vesicles were spherical in shape. The optimized formulation was found to follow zero order release kinetics and korsmeyer-peppas release mechanism. F80H1 found to be non-irritant and stable from skin irritation and stability studies.

Formulation and Characterization of Novel Non-Ionic Surfactant Based Aceclofenac Gel as a Potential Drug Delivery System

Background: Aceclofenac is considered to the first line drug in the symptomatic treatment of rheumatoid arthritis, osteoartheritis and ankylosing spondylitis. The successful treatment of arthritis depend on the maintenance of effective drug concentration level in the body, for which a constant and uniform supply of drug is desired. The short biological half-life (about 4 hrs) and dosing frequency more than once a day as well as (70-80%) of dose is excreted by renal transport make aceclofenac an ideal candidate for formulation of niosomal gel.&#x0D; Methodology: The niosomal gel of aceclofenac in order to sustain the release of aceclofenac topically, decreases the side effect of GI disturbance by maintaining the concentration of the drug in the blood and decrease the renal excretion as well as frequency of dosing. Niosomal gel was prepared by coacervation phase separation method. Preformulation studies, structural analysis, in-vitro drug release study, mechanism of drug release kinetic and data analysis (zero order, first order and higuchi’s model), percentage entrapment efficiency and stability study were performed (n=3). Anti-Inflammatory study was performed for final optimized formulation.&#x0D; Result and conclusion: It is revealed from preformulation studies that materials obtained for study did not show any incompatibility. Particle size was determined in the range of 9.46±1.055 to 12.91±3.587μm by using an optical microscope with calibrated eyepiece micrometer. Scanning Electron Microscopy of niosomes was performed to observe surface morphology and percentage entrapment efficiency of niosomes were reported in the range of 63.49±0.265% to 78.55±0.425%. From release kinetic modelling, it was analysed that the drug was released from niosomes by a diffusion-controlled mechanism. Lastly, stability study of all formulations was done in two different temperature and anti inflammatory activity of final optimised formulation was compared with marketed formulation (Voveran Emulgel). Results shows that the aceclofenac Niosomal gel showed fair anti-inflammatory activity but it was not as good as the commercial product.

Development and Optimization of Proniosomal Gel Containing Etodolac: In-vitro, Ex-vivo and In-vivo Evaluation

Introduction: Etodolac is used in the treatment of acute pain and inflammation. It has low solubility because of high hydrophobicity and it is reported that upon oral administration shows gastric disturbances. This encourages the development of topical vesicular formulation.&#x0D; Method: In this work we used coacervation-phase separation method for the development of etodolac loaded vesicular system by using non-ionic surfactants, cholesterol and soya lecithin. Central composite design (rotatble) was used to optimize the concentrations of soy lecithin, surfactant and cholesterol. The prepared formulations were characterized by number of vesicles formed, vesicle size, zeta potential, entrapment efficiency, in-vitro permeation, ex-vivo permeation and anti-inflammatory study.&#x0D; Results: Etodolac was successfully entrapped in all formulations having efficiency in the range of 74.36% to 90.85%, which was more at 4 °C than room temperature. When hydrated with water; niosome in the range of 54 to 141 (per cubic mm) were spontaneously produced. The results of in-vitro diffusion study revealed that etodolac was released in the range of 71.86 to 97.16% over a period of 24 hrs. The average vesicle size of optimized formulation was found 211.9 nm with PDI of 0.5. The observed responses i.e. % encapsulation efficiency and drug release were 74.12 and 95.08 respectively. The zeta potential was -19.4mV revealed the stability of formulation which was further confirmed by no changes in drug content and drug release after stability studies. The % inhibition in paw volume was 40.52% and 43.61% for test and marketed proniosomal gel.&#x0D; Conclusion: Proniosomal gel formulation was stable and could enhance skin delivery of etodolac because of excellent permeation capability of vesicular system.

Formulation and Evaluation of Topical Proniosomal Gel of Ciclopirox for Antifungal Therapy

Objectives: The objective of existent effort was topical proniosomal gel formulation and evaluation from the proniosomes of Ciclopirox to improve poor skin penetration and residence of the topical antifungal drugs. Methods: The co-acervation phase separation method was used to prepare proniosomes by using combination of different grades of non-ionic surfactant, cholestrol and lecithin. Characterized for pH, encapsulation efficiency, Particle size, in vitro drug permeation. Selected batches were converted into topical proniosomal gel and evaluated for ex vivo permeation. Then best fitted formulation batch C5CF8 were differentiate with marketed preparation for ex vivo drug release and anti-fungal activity. Results: Proniosomal gel pH be there 5.61± 0.25 to 7.31± 0.06 and encapsulation efficiency 82.40 to 92.20% and particle size 3.20 ± 0.15 to 6.45 ± 0.20. In vitro drug release is in between 37.65 to 57.04 %. Among the formulations CF1, CF2, CF3, CF4 and CF5 were developed into carbopol topical gel as C1CF2, C2CF32, C3CF5, C4CF6 and C5CF8 and evaluated for ex vivo drug permeation. Among these optimized formulation C5CF8 showed drug permeation 59.39 ± 0.10 % at 12 hr. with a flux value of 5.24μg/ cm2/hr., permeability coefficient of 0.262 cm2/hr. and higher correlation coefficient R2 0.9949 for zero order drug release and hence follows zero order release kinetics. The C5F8 showed prolonged drug release and zone of inhibition value higher for carbopol gel as compared to marketed preparation Conclusion: Developed carbopol topical gel had potential to act as controlled release drug carrier which prolonged the drug release for number of hours.

Proniosomal Gel for Topical Delivery of Rutin: Preparation, Physicochemical Characterization and In Vitro Toxicological Profile Using 3D Reconstructed Human Epidermis Tissue and 2D Cells.

Rutin (Rut) is a natural flavonol, well-known for its broad-spectrum of therapeutic effects, including antioxidant and antitumoral activities; still, it has a reduced clinical outcome due to its limited solubility in aqueous solutions. To overcome this drawback, this study proposes a novel formulation for rutin as a proniosomal gel for cutaneous applications. The gel was prepared by coacervation phase-separation method and complies with the standard requirements in terms of particle size (140.5 ± 2.56 nm), zeta potential (−27.33 ± 0.09 mV), encapsulation capacity (> 50%), pH (7.002 ± 0.18) and rheological properties. The results showed high biocompatibility of the gel on the 3D reconstructed human epidermis model characterized by increased viability of the cells and a lack of irritant and phototoxic potential. The evaluations on 2D cells confirm the preferential cytotoxic effect of Rut on melanoma cells (IC50 value = 8.601 µM, nuclear fragmentation) compared to normal keratinocytes. Our data suggest that the proniosomal gel is a promising drug carrier for Rut in the management and prevention of skin disorders.

Formulation development, Ex vivo evaluation and In vivo antihypertensive study of losartan potassium loaded nanoproniosomal gel: A novel vesicular approach for transdermal delivery

The transdermal nanoproniosomal gel of Losartan potassium was prepared to treat hypertension that is efficient to deliver the encapsulated drug over extended periods and to provide better bioavailability. In the present study, the nanoproniosomal gel of Losartan potassium was formulated by Lecithin, Cholesterol, Non-ionic surfactants using the Coacervation-phase separation method. The physical mixture of drug, lecithin, and cholesterol were subjected to compatibility study using FTIR spectroscopy. The prepared nanoproniosomal gels were subjected to various evaluation parameters like the determination of pH and viscosity, vesicle size analysis, rate of spontaneity, entrapment efficiency, zeta potential, ex vivo skin permeation studies, skin irritation test, stability studies and in vivo antihypertensive studies. The physical characterization of nanoproniosomal gels was found to be within the acceptable limits. The ex vivo skin permeation studies showed the cumulative permeation of 47.25% to 82.49% through the albino rat skin in 24 hrs for all the formulations which indicate the zero-order drug permeation with diffusion, non-fickian release as the possible mechanisms of drug release. Among all formulations, NLPG2 was selected as best formulation because it showed better characteristics than other formulations in several aspects like entrapment efficiency, vesicle size, ex vivo permeation studies, zeta potential, stability studies, and other evaluation parameters. The selected formulation NLPG2 showed the highest transdermal flux (28.67μg/cm2/h), with an enhancement ratio of 2.87 when compared to other formulations. In vivo antihypertensive study revealed that the formulation NLPG2 was successful to regress the rat BP to normal values in experimental hypertensive rats. Finally, it could be concluded that the formulation NLPG2 accentuates the flux of Losartan potassium and is an efficient transdermal therapeutic system for the delivery of a drug. The nanoproniosomal gels are suitable for once a day controlled release formulation.

A NOVEL VESICULAR APPROACH FOR TRANSDERMAL ADMINISTRATION OF ENALAPRIL MALEATE LOADED NANOPRONIOSOMAL GEL: FORMULATION, EX VIVO EVALUATION AND IN VIVO ANTIHYPERTENSIVE STUDY

Objective: The objective of the study was to formulate and evaluate the nanoproniosomal gel of Enalapril maleate (EM) for the treatment of hypertension through the transdermal administration and to provide better bioavailability.&#x0D; Methods: The nanoproniosomal gel of the EM was formulated by Lecithin, Cholesterol, Non-ionic surfactants using the Coacervation-phase separation method. The prepared nanoproniosomal gels were evaluated for pH and viscosity, vesicle size analysis, rate of spontaneity, entrapment efficiency, zeta potential, ex vivo skin permeation studies, skin irritation test, stability studies and in vivo antihypertensive studies.&#x0D; Results: Physical characterization was found to be within acceptable limits. The ex vivo skin permeation studies showed the cumulative permeation of 58.75 % to 89.72 % through the albino rat skin in 24 h for all the formulations, which indicate the zero-order drug permeation with diffusion, non-fickian release. Among all formulations, EMNP7 was selected as best formulation because it showed better characteristics than other formulations in several aspects like physicochemical characterization, ex vivo skin permeation studies, permeation kinetics, and other evaluation parameters. The skin irritation study revealed that there was no irritation after topical application and it was found to be safer to use. The In vivo antihypertensive study revealed that the formulation of EMNP7 was successful to regress the rat blood pressure (BP) to normal values in experimental hypertensive rats.&#x0D; Conclusion: The nanoproniosomal gel is an efficient transdermal therapeutic system for the delivery of EM for the treatment of hypertension. It is suitable for once a day controlled release formulation.

Proniosomes as a carrier system for transdermal delivery of clozapine

The current study aimed to formulate the clozapine (CLZ) loaded proniosomal (PN) gel and evaluate its in vitro release, ex vivo permeation and gel properties. CLZ is a BCS class II drug with low bioavailability of 27% and severe adverse drug reactions (ADRs) due to frequent dosing. Proniosomes offer a versatile pro-vesicular approach with potential in transdermal drug delivery. PN-CLZ gel was prepared by the coacervation phase separation method utilizing span-60, cholesterol, and lecithin. Optimization of PN gel was done by hit and trial method and the formulations were characterized for particle size, entrapment efficiency (EE), polydispersity index (PDI), and zeta potential (ZP). The optimized formulation had the highest EE of 90% and the average particle size of approximately 325 nm. PDI reflected homogeneity in the formulation. ZP was –59.76 mV, high enough to indicate a stable formulation. The in vitro release studies manifested a sustained release behavior of CLZ from the PN gel. The ex vivo permeation showed noteworthy permeation of the drug through stratum corneum with a steady state flux of 18.26 μg/cm2/h. The optimized gel was analyzed for pH, spreadability, bioadhesion, and rheology. The results suggested that CLZ could be effectively loaded into PN gel for administration through skin.

Formulation, Optimization and In vitro / In vivo Characterization of Spray Dried Doxorubicin Loaded Folic Acid Conjugated Gelatin Nanoparticles.

Formulation, optimization and anticancer activity of spray-dried Doxorubicin loaded folic acid conjugated Gelatin nanoparticles (DOX-FA-GN). Doxorubicin loaded gelatin nanoparticles (DOX-GN) were prepared by the Coacervation phase separation method, optimized using DoE and then conjugated with folic acid by covalent coupling to formulate Doxorubicin loaded folic acid conjugated nanoparticles (DOX-FA-GN). The formulated nanoparticles were characterized to evaluate its physicochemical properties. Cellular uptake and cell viability studies were carried out using MTT assay and biodistribution studies were carried out in Wistar rats. Particle size, PDI and entrapment efficiency for optimized DOX-GN were found to be 152.3 ± 9.3 nm 0.294 ± 0.1 and 86.9± 3.4% while for DOX-FA-GN, 193.9 ± 12.3 nm 0.247 ± 0.2 and 84 ± 3.6%. The cytotoxic studies showed a cell viability of 75.1% for DOX-GN and 29.5% DOX-FA-GN. Biodistribution studies were found to be statistically insignificant for conjugated nanoparticles with excellent flow properties. Significantly higher DOX distribution in the lungs was observed in the case of DOX-FA-GN. There was a higher uptake of DOX on HeLa cells with DOX-FA-GN compared to DOX-GN. Also, the biodistribution of Dox in the lungs of Wistar rats was higher in conjugated nanoparticles as compared to unconjugated nanoparticles.