Eudragit RSPO Research Articles

Gastroretentive bilayer film for sustained release of atorvastatin calcium and immediate release of amlodipine besylate: pharmaceutical, pharmacokinetic evaluation, and IVIVC

The present study was aimed to optimize capsulated unfolding type gastroretentive bilayer film constituting immediate release (IR) layer of amlodipine besylate and sustained release (SR) layer of atorvastatin calcium. A three-factor, three-level Box–Behnken-design was used to optimize bilayer film with dual-release characteristics. The selected independent variables were HPMC-K3, Eudragit RSPO, and Carbopol 934P and the responses were floating duration, swelling index, and in vitro release from SR layer in 8 h. The films were also assessed for pharmacotechnical characteristics, release kinetics, DSC, FTIR, and SEM. The pharmacokinetics of the drugs from the optimized formulation was compared with the marketed formulation in rabbits. The capsulated accordion film unfolded and provided SR of atorvastatin for 8 h (96.76% ± 0.71) and IR of amlodipine within 25 min (98.07% ± 0.62) for the optimized formulation (F14). The swelling index and floating duration for the optimized formulation were 140.48 ± 0.57 and 8.53 ± 0.10 h, respectively. Results of pharmacokinetics showed that faster absorption of amlodipine and improved bioavailability (2.16-fold) of atorvastatin in blood was made available through bilayer film. In vitro–in vivo correlation was established using numerical deconvolution method. It can be concluded that the capsulated gastroretentive system provided site specific simultaneous SR of antihyperlidemic drug and IR of antihypertensive drug as single pill that has therapeutic potential to manage cardiovascular risk.

The Preparation of Curcumin Sustained-Release Solid Dispersion by Hot Melt Extrusion—Ⅰ. Optimization of the Formulation

The purpose of this study was to optimize the formulation for developing curcumin sustained-release solid dispersion to increase the solubility of curcumin, delay drug release by hot-melt extrusion, and to explore the possibility of hot-melt extrusion for one-step preparation of insoluble drug sustained-release solid dispersion. The miscibility of curcumin and Eudragit RSPO and Eudragit RLPO were assessed by solubility parameter and melting point depression. Orthogonal test was used to optimize the formulation, based on the results of single-factor experiment, and the final optimal formulation: the ratio of the sustained-release carrier material RS/RL was 1:3, the ratio of drug and carrier was 1:6, and the porogen was used in an amount of 40% of the sustained-release carrier material. The curcumin solid dispersion of the best formulation had been prepared and had a significant sustained-release effect compared to the curcumin and the physical mixture.

A review on polymers in natural or modified form used in sustained release tablet

Tablet is a solid dosage form which is used to deliver the drug to the body to make pharmacological action. The oral dosage form should disperse into small particles to deliver active ingredients in the body, the disperse time of the dosage form depends on the ingredients which are used in the tablet. To make the tablet disintegrate slow usually sustained release agents are used. The sustained release tablets helps in maintaining the drug concentration in the body for the higher time. In this review article various polymers of natural origin and their modified forms are studied, which can be used in the sustained release tablet. In this review article the polymers studied were, Psyllium husk, HPMC K100M, Cellulose polymers, Cellulose ether polymers, Xanthan gum, Guar gum, Eudragit RLPO, Eudragit RSPO, Eudragit RL 100, Eudragit RS 100, Kollidone SR and Carnauba wax. Now a day the sustained release tablets are used more than the conventional tablets because of the patient incompliance. The main part of the sustained release tablets are the polymers. In the study it was found that the modified forms of natural polymers works better than in their natural form. In the study it was found that the hydrophilic polymers also work better like Xanthan gum and Guar gum, they are effecting and non-toxic in nature. The cellulose derivatives were studied and it was found that Substituted cellulose-methylcellulose, hydroxypropylcellulose and hydroxypropylmethylcellulose works better in the combination form. Keywords: Sustained release, Xanthan gum, Guar gum, Eudragit, Kollidone, HPMC

Preparation and Characterization of Itraconazole Microsponges using Eudragit RSPO and Study the Effect of Stirring on the Formation of Microsponges

The purpose of the present study was to prepare and evaluate Itraconazole loaded microsponges using Eudragit for the controlled release of the drug and study the effect of stirring rate on the formation of microsponges. Microsponges containing Itraconazole were prepared by using quasi-emulsion solvent diffusion method at different stirring rate i.e. 500, 800, 1000, 1200 and 1500rpm. Particle size of prepared microsponge was observed in the range of 78.43 to 23.18 µm. Scanning electron microscopy revealed the porous, spherical nature of the microsponges. The production yield, entrapment efficiency, and drug content were found to be 80.88%, 84.53% and 82.89%. The formulation with higher drug to polymer ratio 1:10 (i.e. F5) was chosen to investigate the effect of stirring rate on the morphology of microsponges. As the speed was increased, the particle size of microsponges was reduced and uniform spherical microsponges were formed. As drug polymer ratio increased, Production yield, drug content and entrapment efficiency was found to be increased while drug: polymer ratio has reverse effect on particle size, as drug: polymer ratio increase, particle size decreases. The cumulative percentage drug release upto 8hrs for F5 was 89.54% and the mechanism of drug release from the formulations during the dissolution was determined using the zero order, first order, higuchi equation and Peppas equation. All formulations were best fitted to Zero order and peppas plot. The best formulation F5 follows Zero order release. Keywords: Microsponges, Itraconazole, stirring rate, Quasi-emulsion solvent diffusion method

Study of the critical points in combined matrix tablets containing both inert and swelling excipients

This work estimates for the first time critical points in combined matrices containing varying concentrations of the hydrophilic polymer Hydroxypropyl methylcellulose (HPMC) K100 M CR in presence of a constant percentage of the inert matrix forming polymer Eudragit RS-PO as well as varying concentrations of the inert polymer in presence of a constant percentage of the hydrophilic excipient. Drug release assays, water uptake studies and calculation of the Exicipient Efficiency (EE) have been carried out to study the interaction between the polymers.Surprisingly, an increase in the drug release rate occurs as the percentage of the hydrophobic polymer increases in the formulations. This fact is supported by the EE values which indicate a negative interaction between the two excipients. Moreover the HPMC percolation threshold estimated is higher than the one observed in pure HPMC matrices.It can be concluded that the HPMC creates pores in the inert skeleton, destabilizing the system. Moreover, the inert excipient destabilizes the gel layer formed by HPMC, changing its critical point. This information is essential for a rational estimation of the Design Space of a formulation and provides new knowledge on the behavior of the polymers in combined matrices, which contributes to the science based design.

Combining amorphous solid dispersions for improved kinetic solubility of posaconazole simultaneously released from soluble PVP/VA64 and an insoluble ammonio methacrylate copolymer

The aim of this study was to evaluate the potential of combining multiple ASDs based on water soluble and insoluble polymers to reach and maintain poorly soluble posaconazole (PCZ) supersaturation over time. ASDs of PCZ were obtained with PVP/VA64 or an ammonio methacrylate copolymer by solvent evaporation method with a fixed 20% (wt/wt%) drug loading ratio and physical mixtures of these ASDs were prepared at various proportions. ASDs were characterized by Fourier transform infrared spectroscopy (FT-IR) and powder X-ray diffraction (PXRD) and compared to their respective physical mixture with crystalline PCZ. Crystalline PCZ equilibrium solubility was determined at pH 1.2–2 range. Dissolution profiles were constructed under non-sink condition with an adapted dissolution system. PXRD analysis demonstrated that both ASDs were at the amorphous state and FT-IR spectroscopy revealed that the analytical signal of PCZ was also absent in both ASDs. Equilibrium solubility of crystalline PCZ varied between 26.36 ± 0.32 (pH 2) to 609.33 ± 3.68 (pH 1.2) μg/mL. All ASDs reached higher concentrations than the equilibrium solubility of crystalline PCZ during dissolution. PVP/VA64 ASDs showed dominance over PCZ dissolution and recrystallization rates whereas Eudragit RS PO ASD alone did not cause PCZ recrystallization whatsoever. The combination containing 20 mg PVP/VA64 + 80 mg Eudragit RS PO as PCZ carriers obtained the highest AUC, suggesting that even after the PVP/VA64 part was completely dissolved, reaching a concentration above crystalline PC Cs, the insoluble polymer could still release PCZ slowly and maintain supersaturation over time. The research demonstrated a potential of combining multiple ASDs to achieve distinct dissolution profiles while increasing the kinetic solubility of poorly soluble drugs.

Emerging role of polyethylene glycol on doxycycline hyclate-incorporated Eudragit RS in situ forming gel for periodontitis treatment

Phase separation with solvent exchange induced-in situ forming gel (ISG) is an attractive delivery system for periodontitis treatment. Eudragit® RS-PO (ERS) in N-methyl pyrrolidone (NMP) was used as polymer matrix for doxycycline hyclate (DH)-loaded solvent-exchanged ISG; however, a high burst drug release was evident. The present study revealed the role of PEG 1500 on physicochemical properties and modification of a burst release for DH-loaded ISG. DH-loaded ISG system comprising PEG 1500 exhibited the Newtonian flow with acceptable injectability with PEG 1500 concentration dependence and high in vitro degradation owing to NMP and PEG 1500 liberation. Solvent exchange between NMP with PBS pH 6.8 conveyed the rapid phase separation of ERS/PEG 1500 as a matrix which the entrapped DH diffused out gradually. Both dialysis membrane and membrane-less methods proved the slower drug release of DH-loaded ERS ISG comprising PEG than PEG 1500-free ISG. SEM revealed the porous matrix topography from polymeric phase separation especially for higher PEG 1500 loading. PEG 1500 incorporation significantly decreased the inhibition diameter against S. aureus, E. coli and S. mutans (P < 0.05) indicating the retardation of drug release owing to the high viscosity of the PEG 1500. PEG 1500-incorporated DH-loaded ERS ISG exhibited the potential use for periodontitis treatment. PEG loading into solvent induced ERS in situ forming gel for doxycycline hyclate periodontal pocket delivery.

Formulation, Evaluation and Optimization of Transdermal Drug Delivery System of Methotrexate Using Different Ratio of Eudragit RLPO / RSPO

The present investigation was aimed to development, evaluation and optimization of transdermal preparations capable of administering Methotrexate (MTX), which is at present considered to be most effective for rheumatoid arthritis, more safely than conventional oral preparations while permitting high compliance. Transdermal patches of Methotrexate were prepared by solvent casting method using Eudragit RLPO: Eudragit RSPO in different ratios along with Di butyl -n- phthalate as plasticizer. MTX containing transdermal patches were formulated by using central composite design having 2 independent variables at 3 levels. Independent variables were total amount of polymers (X1) and % of Eudragit RSPO (X2). The prepared formulations were evaluated for various physicochemical properties like flexibility, thickness, smoothness, weight variation, Tensile Strength, Folding Endurance and Drug Content and was found to be flexible, smooth, uniform thickness and weight, suitable drug content (98 to 99.9 %) and good Folding endurance (> 100). The prepared formulations were also evaluated for in-vitro drug release and Ex-Vivo drug diffusion characteristics. Statistical Optimization carried out for various responses like ‘K’ of zero order, T50% and T80%. Optimized Formulation was found to provide more controlled diffusion of drug. Release kinetics of Optimized Formulation followed zero order drug diffusion. Hence Optimized Transdermal Patch could be a promising delivery system for Methotrexate with sustained release action and improved drug availability.

FORMULATION AND EVALUATION OF LORNOXICAM MICROSPONGES USING EUDRAGIT RS 100 AND EUDRAGIT RSPO

Objective: The objective of the present study was preparation and evaluation of lornoxicam microsponges to prolong their drug release up to 12 h for effective osteoarthritis, rheumatoid arthritis, and acute lumbar-sciatica therapy.Methods: Lornoxicam microsponges were prepared by the quasi-emulsion solvent diffusion technique using different concentrations of polymers such as Eudragit RS 100 and Eudragit RSPO in ethanol and dichloromethane organic solvent mixture. Microsponges were evaluated for their particle size, percentage yield, entrapment efficiency, scanning electron microscopy (SEM), and in vitro drug release studies.Results: The percentage yield, entrapment efficiency, average particle size, and in vitro drug release for optimized formulation F12 were found to be 70.23% w/w, 81.34% w/w, 172.72 μm, and 96.64% up to 8 h, respectively. From SEM, it was observed that microsponges were found to be spherical in shape with rough surface texture. The formulation F12 shows zero-order release kinetics with an r2 value of 0.961 and the value of Korsmeyer–Peppas model was found to be 0.792; it follows super case II non-Fickian diffusion. The in vitro drug release studies showed that formulations comprised varying concentrations of Eudragit RSPO in higher proportion exhibited much-retarded drug release as compared to formulations comprised a higher proportion of varying concentrations of Eudragit RS 100.Conclusion: Among all the formulations F12 shows better results, which are released more than 80% of the drug release within 8 h; hence, it is optimized. These developed microsponges are releasing the drug for a longer period, which will be effective for osteoarthritis, rheumatoid arthritis, and acute lumbar sciatica therapy.

Formulation and In vitro Evaluation of Unfolding Type Expandable Gastroretentive Film of Enalapril Maleate

The present work was based on the development and characterization of unfolding type gastroretentive dosage form appropriate for controlled release of enalapril maleate. Drug loaded films were prepared by solid dispersion technique using methocel K15 and eudragit RSPO and eudragit RLPO as polymers and polyethylene glycol 400 (PEG 400) as the plasticizer. The film folded in a capsule shell was shown to unfold in the gastric juice and provide drug release up to 12 h in the acidic medium. Formulations provided satisfactory unfolding characteristics allowing expansion to remain in the stomach. Formulation containing above 60% content of eudragit RSPO and eudgrait RLPO combination of total polymer content provided satisfactory film integrity over 12 hours. The result revealed that formulation F1 showed a minimum percentage of drug release of 63.41% followed by formulation F2, F3, F4 and F5 with 66.76%, 80.21%, 83.26% and 86.92% release in 8 hour respectively. Formulation with high proportion of eudragit RLPO and RSPO combination in total polymer content was found to be slow in drug release and lower the release from the polymeric film over time. As the concentration of HPMC K 15 in total polymer content increased the release rate of enalapril maleate as well as % release from the polymeric film also increased over time. Most of the formulation followed Higuchi release kinetics followed by Korsmeyer release kinetics. The drug release mechanism from the film follows Fickian and Non Fickian release kinetics. The films were evaluated for mechanical properties, in vitro drug release and unfolding behavior based on the mechanical shape memory of polymers. Absence of drug polymer interaction and uniform drug dispersion in the polymeric layers was revealed by DSC, FT-IR and SEM studies.Bangladesh Pharmaceutical Journal 20(2): 148-154, 2017

Nifedipine di-matrix depot tablets prepared by compression coating for obtaining zero-order release

Compression coating is a possible process for obtaining zero-order release. Nifedipine compression-coated (CC) di-matrix depot tablets were prepared from a single punch tablet press with low viscosity hydroxypropyl cellulose (HPC-L) as the inner polymer, and with middle viscosity hydroxypropyl cellulose (HPC-M), HPC-L and Eudragit RSPO as outer polymers. The release behavior and mechanisms in vitro of the final tablets were investigated, and gravimetric analysis was used to study the release mechanism. The fast release of the core depot and slow release of the outer depot with time formed total zero-order release. The results showed that the formulation presented ideal zero-order release at the weight ratio of nifedipine 3:5 (core: layer), the combination of HPC-L and HPC-M (56:25) in the outer depot, and with the core depot placed in the center. The CC tablets released to more than 95% in 24 h and fitted a zero-order model with the equation Mt/M∞ = 0.038t (R2 = 0.98555). In conclusion, zero-order release of nifedipine over 24 h could be achieved by applying polymer HPC-L and HPC-M with the compression coating technique.

Formulation Optimization and Study on Effect of Penetration Enhancers on Reservoir Transdermal Therapeutic Systems of Hydralazine Hydrochloride

: Background: Hydralazine hydrochloride (HZH) is a drug candidate used to treat pulmonary arterial hypertension. Extreme variability in oral dosing, bioavailability of 31%, variable half-life of 3 to 7 h and molecular weight of 196.6 Daltons, made the drug molecule suitable for transdermal system. Objective: The objective of the present investigation is to study the effect of penetration enhancers on release kinetics of hydralazine hydrochloride both in vitro and in vivo through reservoir based transdermal systems. Materials and Methods: Rate controlling membranes were formulated by using HPMC, Eudragit RLPO and Eudragit RSPO. Reservoir was formulated by using 16% poloxamer 407 gel by cold method as it is having sol-gel temperature at 37°C. Results and Discussion: The drug release followed zero order non-fickian super case-II diffusion transport mechanism. Enhancement ratio was more with IPM as penetration enhancer. Formulation F7 had maximum in vitro release of 95.68 ± 1.16% with flux value of 64.168±0.071 μg/h/cm2, no significant difference in ex vivo permeation study was observed. The fabricated reservoir system was found to be safe for skin. In vivo kinetic studies projected a controlled release pattern with extended AUC of 25.760 ± 9.124 μg/mL/h with MRT 17.7 ± 0.37 h in transdermal route compared to oral route where AUC and MRT are 4.409 ± 2.015 μg/mL/h and 2.98 ± 1.24 h respectively. Conclusion: The drug reservoir transdermal system of HZH had varied in vitro release profile with varying the concentrations of penetration enhancer. The optimized transdermal system had extended AUC and MRT values compared to oral route and can enhance the bioavailability.Key words: Hydralazine hydrochloride, Isopropyl myristate, In vitro kinetics, In vivo kinetics, Poloxamer 407.

Development and Evaluation of Mesalamine—Glutamine Cocrystal Tablets for Colon Specific Delivery

&#x0D; The objective of the work was to develop the co-crystal formulation of mesalamine with glutamine. It was done to enhance dissolution rate, solubility and physicochemical properties to be used in pharmaceutical composition (tablet) for colon targeting. Co-crystal preparation was carried out by liquid assisted grinding method using glutamine as a co-crystal former (1:1 stoichiometric ratio) and acetonitrile as a solvent giving maximum solubility and dissolution rate. The formation of the co-crystals was confirmed by Fourier Transform – Infra Red spectrometry, Differential Scanning Calorimetry and Powder X-Ray Diffraction. Pre-compression studies included measure-ment of bulk density, tapped density, angle of repose, Hausner’s ratio and compressibility index. The tablets were prepared by direct compression. Post compression parameters for uncoated tablets included hardness, size and thickness, friability and weight variation. Enteric-coated tablets were prepared by dip-coating process using Eudragit RSPO, Triethyl citrate and isopropyl alcohol mixture as coating solution. The coated tablets were further evaluated for disintegration and dissolution testing. All the results were found to be under specified limits. Finally, co-crystal tablets were compared with marketed formulation. In vitro dissolution rate of optimized mesalamine co-crystal tablet was comparatively higher than marketed formulation, which reflects improvement in solubility. Glutamine has good anti-inflammatory property. Formulation with glutamine as co-crystal added more efficacies to mesalamine for treatment in colon related inflammatory diseases. It was concluded that stable co-crystals of mesalamine -glutamine having better anti-inflammatory property, increased solubility and improved in vitro dissolution of mesalamine can be successfully prepared. &#x0D;

A novel co-processed directly compressible release-retarding polymer: In vitro, solid state and in vivo evaluation

Directly compressible (DC) co-processed excipient capable of providing nearly zero order release with improved functionality was developed without any chemical modification by employed various techniques such as physical mixing, high shear mixer granulation and spray drying. Co-processed excipient was developed by using release retarding polymer Eudragit RSPO, separately, in combination with different concentration of hydroxyl propyl methyl cellulose 100 cps (Methocel K100 LV, HPMC), ethyl cellulose (Ethocel N50, EC) and hydroxyl propyl cellulose (Klucel EF, HPC). All co-processed excipients were evaluated for their flow properties in terms of angle of repose, bulk density, tapped density, compressibility index and Hausner's ratio. Out of eighteen combinations, the nine co-processed excipients exhibited promising flow properties were found suitable for direct compression and formulated as tablets. Metoprolol succinate, a BCS Class I drug, was selected as a model drug and the formulation was developed employing direct compression approach. The developed tablets were evaluated for physical parameters like uniformity of weight, thickness, hardness, friability and assay. In vitro dissolution study confirms that formulation prepared using co-processed excipient showed sustained drug release. The optimized tablet formulation was characterized by DSC, FTIR and PXRD which confirms the absence of any chemical change during co-processing. The optimized formulation was kept for stability study for six months as per ICH guidelines and found to be stable. In vivo pharmacokinetic study of optimized formulation in rats showed similar pharmacokinetic behaviour as was observed with the marketed brand. Study revealed that co-processed excipient has advantage over polymers with single property and can be utilised for sustained release formulation.

Formulation, development and evaluation of film-forming gel for prolonged dermal delivery of miconaole nitrate

The localized treatment of diseases of body tissues requires that the pharmaceutical active be maintained at the site of treatment for an effective period of time. Sweat, clothing, movements and getting washed away easily on contact with water are some of the problems that have limited the effectiveness and residence time of conventional topical formulations for treatment of fungal infections of skin. This necessitates longer treatment duration. Hence, a composition that adheres to skin surface afflicted and provides localized delivery of an antifungal agent is needed. The present work aims at designing a dosage form of Miconazole nitrate referred to as a ‘film-forming gel’ which on application forms a thin, transparent film on skin surface. Eudragit RS PO and hydroxypropyl cellulose were used in combination to provide a matrix film that would permit the release of the antifungal agent for a prolonged time. The formulations were prepared using 32 full factorial design. They were tested for drying time, drug release, antifungal activity, skin irritation and stability studies. The gel was characterised for pH, viscosity, drug content, effective dosage volume and mechanical properties of the film formed after application; water vapour permeability were also tested. All the formulations showed results within acceptable range for various tests. The optimized formulation showed drug release of 99.76% and antifungal activity in terms of efficacy as 98.78%. Such a formulation can be claimed to decrease duration of therapy, will be more accepted by the patients and be a breakthrough in treating fungal infections of the skin.

Design and Pharmacodynamic Evaluation of Optimized Microporous Osmotic Tablets of Venlafaxine Hydrochloride

Microporous osmotic tablets were developed using controlled porosity membrane, which delivers drug in a controlled manner for prolonged period of time. The objective of the present investigation was to formulate and evaluate an oral osmotic drug delivery system for the antidepressant drug venlafaxine hydrochloride to achieve zero order release. Venlafaxine hydrochloride was selected as it has a short biological half-life and high aqueous solubility. Drug-excipient compatibility was studied using Fourier transform infrared spectroscopy. Core tablets were prepared by wet granulation method followed by coating. Sodium chloride and potassium chloride (1:1) were used as osmotic agents in the core tablet and polymers Eudragit RLPO and RSPO (1:1) were used for coating along with sorbitol (70% w/w) as pore formers. The tablets showed desired sustained release profile for 24 h. Optimization studies were performed to study the effect of concentration of osmotic agent and pore former on drug release (t50% and t90%). From in vitro release studies, it was evident that drug release was independent of dissolution media, agitation intensity, but highly dependent on the concentration of pore forming agents, osmotic agent and weight gain of the tablet coating. Scanning electron microscopy confirmed the microporous structure of optimized batch. The optimized formulation gave desired once a day release of venlafaxine hydrochloride without using laser drilling technique which would make it more patient compliant and cost effective.

Formulation of Bilayer Benzydamine HCl Patch Targeted For Gingivitis

In the present study bilayer patch of benzydamine HCl was developed using solvent casting method. Different substrates were attempted like Petri dish, glass-and-ring, and teflon-and-ring for selection of the proper option to formulate patch that should give easily peelable film with adequate mechanical properties. HPMC E15 LV was used in different concentrations for obtaining proper viscosity of solution for pouring on to surface and ring, that it should not leak from ring. The second layer was optimized by using different polymer like eudragit RSPO, eudragit RSPO + EC, and eudragit NE30 D for efficient layer bonding. The minimum release from backing membrane was established by diffusion study as compared to from drug loaded layer. The optimized batches were evaluated for folding endurance, weight variation, thickness, drug content, drug release, tensile strength, layer separation, mucoadhesion, moisture uptake, and layer bonding. The novel gingival patch of benzydamine HCl developed would be beneficial in optimizing the therapy.

Hot melt extruded transdermal films based on amorphous solid dispersions in Eudragit RS PO: The inclusion of hydrophilic additives to develop moisture-activated release systems

A series of Eudragit RS PO-based hot melt extruded films were evaluated as potential transdermal systems, with particular emphasis on the inclusion of hydrophilic excipients to allow water sorption, which in turn would allow drug release on application to the skin. More specifically, sucrose, methyl cellulose, xanthan gum (Xantural®75), poloxamer (Pluronic®F127), Gelucire 44/14 were added to Eudragit RS PO and assessed in terms of physical structure (modulated temperature DSC (MTDSC), thermogravimetric analysis (TGA), powder XRD (PXRD), scanning electron microscopy(SEM)) and in vitro drug release and permeation properties. In addition, the effect of prior hydration on drug permeation was studied for selected systems. Phase separation was noted for sucrose, methylcellulose (high loading), xanthan gum (high loading), poloxamer and Gelucire 44/14 (high loading) using both visual observation and MTDSC. PXRD studies indicated drug crystallization within the phase separated systems. SEM studies broadly followed the same pattern. Dissolution studies indicated that the hydrophilic excipients considerably enhanced the release rate, while Franz diffusion cell studies showed a much greater variability in effectiveness, which we ascribe to the paucity of water of hydration present which would not allow swellable additives such as xanthan to release the drug. However, films containing Gelucire 44/14 emerged as the most satisfactory systems, despite the higher additive loaded systems showing drug phase separation. This may be related to emulsification rather than swelling on contact with water, as noted for the permeation studies involving pre-hydration. This strategy therefore presents a promising approach for triggered transdermal drug delivery, activated by hydration from the skin itself.

Development and characterization of solid dispersion-microsphere controlled release system for poorly water-soluble drug.

The present study aimed to improve solubility and prolong the release duration of a poorly soluble drug using a combination of two different types of formulations (solid dispersion and microspheres). The solid dispersions were prepared by fusion method using urea and mannitol as hydrophilic carriers. Microspheres were prepared by solvent evaporation method using Eudragit L-100 (EL100) and Eudragit RS PO (ERS) as rate-controlling polymers. Flurbiprofen (FBP)-urea (1:2) solid dispersion and microspheres of FBP-EL-100-ERS (1:0.25:0.75) were used for the development of controlled release formulation by mixing them in different proportions. The FBP-containing formulations were evaluated for percentage yield, drug content, morphology, in vitro release, and in vivo anti-inflammatory activity. The best selected formulation was further evaluated for the controlled and improved effects. SEM photomicrograph confirmed the spherical shape of microspheres and with particle size in the range of 73.5-85.4μm. In vitro release of FBP from controlled release formulations indicated that the formulation containing solid dispersion:microspheres (1:0.5) yielded prolonged effect up to 10h. The release kinetics followed zero-order, and the mechanism of drug release was found to be diffusion rate controlled. This formulation had shown better inhibition of edema of rat paw up to 16h and identified as a suitable product for controlled delivery of FBP. In conclusion, the concept of using a binary mixture of solid dispersion and microspheres can be used for other drugs that exhibit a poor solubility in stomach pH and a faster release in intestinal pH.

Heterogeneous polymer composite nanoparticles loaded in situ gel for controlled release intra-vaginal therapy of genital herpes

Herpes simplex virus causes serious and contagious genital infections in high percentage of female population world-wide. Acyclovir is a clinically successful antiviral molecule till date, in-spite of limitations as poor solubility, low half-life, reduced oral bioavailability and side effects at higher doses. In the present work, controlled release in situ gelling system loaded with polymeric nanoparticles of acyclovir containing a dose of drug equivalent to 105mg/day has been developed. The formulation containing drug loaded polyvinyl pyrrolidone⿿Eudragit RSPO hybrid polymeric nanoparticles (Size ⿼99±3nm, Zeta ⿼+26.1±1.5mV) in 15% Pluronic F-127 gel exhibited improved permeability through vaginal membrane (KP=2.20±0.19ÿ10⿿6cm/s). The nanoparticles showed enhanced viability for vaginal epithelial cell lines up to concentration of 100⿿250μg/mL. The formulation was evaluated for bioavailability and biodistribution through intra-vaginal administration in rat models. The nanoparticle in situ gel formulation maintained an average therapeutic drug level of 0.6±0.2μg/mL in plasma for 24h. Significant improvement in mean residence time of the drug (12.52±1.12h) was observed with a two-fold increase in the relative bioavailability (AUC0⿿24h=14.92±2.44μgh/mL) compared to that of the pure drug (7.18±1.79μgh/mL). The tissue distribution was 2⿿3 folds higher in animals treated with nanoparticles in situ gel compared to that of pure drug. Sustained release of drug in vivo was demonstrated, ensuring the suitability of the formulation for clinical therapy in female population.