Exploring paediatric oral suspension development: Challenges, requirements, and formulation advancements.

Oral suspension is the most preferred dosage form for the paediatric population because of the difficulties related to solid medications, such as the swallowing limitations, bitter taste, and poor oral bioavailability, which can cause serious impairment to attain a successful treatment. Given the importance of successful therapies, there is a need for safe and effective commercially-available paediatric oral suspension and their characterization. For the latter, it is important to identify safe excipients and preservatives. The paediatric group is a diverse category which includes infants and teenagers, with major pharmacokinetics and pharmacodynamics differences, mainly because of physiological and behavioral variations. Therefore, finding a single formulation for paediatric population remains a challenge, as well asthe formulation of stable-in-time suspension. In addition, drug's dissolving characteristic and permeation, are the main determinants for oral absorption, which are closely related to drug release kinetics from the pharmaceutical form. In this context, drug release profile is an important and limiting step in oral bioavailability, particularly for BCS class II drugs; thus, it is possible to increase bioavailability and minimize adverse effects by changing the release rate of such drugs. This review covers all the aspects for paediatric oral suspension development, and analyses the considerations for excipients selection as a crucial task for effectively choosing a safe and effective pharmaceutical form and correctly dosing paediatric patients.

Application of Tablet in Tablet technique to design and characterize immediate and modified release tablets of Timolol maleate.

Hypertension is one of the major causes of mortality in the world. The non-selective -ß-blocker which includes Timolol maleate (TM) is usually used in hypertension, at a given dose of 10-40 mg. The present research aims to design a tablet-in-tablet (TIT) formulation as a single-unit dosage form to achieve modified and rapid drug release. Wet granulation was used to create the inner core modified release tablet utilising the release modifying agent's Sodium alginate (SA) and Hydroxypropyl methylcellulose (HPMC K4M). The impact of independent factors, SA and HPMC K4M, in different percentages of w/w, which affect the in vitro drug release and swelling index, was investigated using a 32 complete factorial design. The TM outer instant-release shell, which was made using croscarmellose sodium and Microcrystalline cellulose (MCC) in three distinct sizes, was press-coated onto the optimised inner core tablet. The core and outer shell tablets are within acceptable ranges for several physicochemical properties. No indication of interactions between drugs, polymers, and excipients was found in the Fourier transform infrared (FTIR) and Differential scanning calorimetry (DSC) investigations. The inner core tablet's formulation F6 achieves a 96.38% in vitro drug release at 24 h and a swelling index of 52.7%. The TIT-2 was, however, considered as the final tablet-in-tablet formulation because contains fewer excipients and shorter disintegration time than TIT-3.

Potential therapeutic effects of naringin loaded PLGA nanoparticles for the management of Alzheimer's disease: In vitro, ex vivo and in vivo investigation.

Background: Alzheimer's disease (AD) is the most prevalent type of dementia which has been affected to more the 44 million people globally. It is distinguished by gradually deteriorating memory and other cognitive abilities that precede dementia. Present treatment of AD mainly focuses on symptomatic slowing the evolution of the disease which is associated with numerous side effects such as dizziness, tiredness, nausea, vomiting, heart attack, and stroke etc. Henceforth; there is urgent need to identify the alternative treatment for management of AD. Herbal medicines have been used from long time to treat AD. One of such leading Phyto molecule is Naringin. It showed promising results against AD but suffers from poor bioavailability and require in high dose to cross the blood brain barrier. Objectives: The main objectives of proposed work are to increase the bioavailability of naringin in brain by developing Nano-suspension and preclinical evaluation of neuroprotective effect of Naringin Nano-suspension (NNS) against Scopolamine induced Alzheimer's disease in rats. Methods: The present study deals with the development, characterization of NNSand to evaluate neuroprotective effect of NNS. Nanoparticles of drug were formed by using PLGA polymer and optimized by using 32 factorial design. Optimized batch was further characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Further the effectiveness of NNS was preclinically investigated by performing AOTstudy as per OECD guideline 420. AD induced Albino Wistar Rats were treated with NNS orally for 14 days and then evaluated for parameters like Gross examination of brain, Relative brain weight determination, behavioural parameters, neuro-inflammatory parameters and immune-histology. Results: Optimization was carried out to study the effect of polymer concentration and number of HPH cycles on Particle size, Poly dispersity index (PDI) and % entrapment efficiency. Desirability search approach was used to select the optimized formulation. Based on the selection criteria, batch F6 having 357.6 ± 05 nm particle size, 0.168 ± 0.04 PDI and 91 ± 2% EE was selected as optimized batch. SEM analysis showed spherical morphology and XRD confirmed the molecular dispersion. Pre-treatment with NNS showed neuroprotective activity basedon results of behavioural studies, biochemical estimation, neuroinflammatory parameters and immunohistochemistry evaluations. Conclusion: As NNS showed significant neuroprotective and anti-neuro-inflammatory effect, this study opens up new ways to exploit Naringin for various therapeutic and restorative purposes.

Overview of phytosomes in treating cancer: Advancement, challenges, and future outlook.

One of the major causes of death on the globe is cancer. It has remained a significant obstacle for current therapies and has not yet been effectively treated. Conventional treatment strategies available for cancer such as surgery, chemotherapy, radiation therapy etc. have severe adverse effects. The use of herbal active constituents in cancer treatment has tremendous potential to increase the effectiveness of conventional cancer therapy. Natural plant active components have been reported to have strong in vitro pharmacological activity but narrow in vivo absorption. In order to increase their bioavailability and absorption and get around the drawbacks and negative effects of traditional herbal extracts, Phytosomes are one of the growing nanotechnologies that can be used to improve the miscibility of bioactive phytoconstituents in lipid-rich barriers and overcome their poor bioavailability. Many novel drug delivery carriers are employed for targeted delivery of phytoconstituent at the site of action. Phytosomes are well-known biocompatible nanocarriers that can be employed to increase the solubility and permeability of phytopharmaceuticals among various novel drug delivery systems (NDDS). This review mainly focused on various conventional as well as novel approaches and various Nano carrier used in cancer therapies. Also comprising summary of the most recent research on the development and use of phytosomes as a better carrier for herbal constituents in the treatment of cancer. Additionally provides information about the formulation, characterization technique and mechanism of drug release from phytosome. Some of the major herbal active constituents made of phytosome which have shown proven anticancer activity are also studied. Finally, challenges and future perspective related to phytosome in cancer treatment are also discussed.

Dry Powder Inhaler with the technical and practical obstacles, and forthcoming platform strategies.

A Dry Powder Inhaler (DPI) is a technique as well as a device used to inhale formulation which is in the form of dry powder, and is inhaled through the nose or mouth. It was developed for the purpose of treating conditions like chronic obstructive pulmonary disease (COPD), Asthma, and even cystic fibrosis etc. The aim of the review is to discuss the different methods of preparation of dry powders along with the characterization of DPI. Here we present the outline of different methods like supercritical fluid extraction (SCF), spray drying, and milling. The review focussed on various devices including single and multi-dose devices used in the DPI. It also highlights on recent advances in the DPI including nano particulate system, siRNA-based medication, liposomes, and pro-liposomes based delivery. In COVID-19 silver nanoparticles-based DPIs provide very prominent results in the infected lungs. Moreover, this review states that the AI-based DPI development provides and improvement in the bioavailability and effectiveness of the drug along with the role of artificial neural networks (ANN). The study also showed that nasally administered drugs (nose to brain) can easily cross the blood-brain barrier (BBB) and enter the central nervous system (CNS) through the olfactory and trigeminal pathway which provides effective CNS concentrations at lower dosage. It is suggested that DPIs not only target respiratory complications but also treat CNS complications too. This review provides support and guides the researcher in the recent development and evaluation of DPI.

An overview of the implementation of SeDeM and SSCD in various formulation developments.

The Sediment Delivery Model explains experimental analysis and quantitative assessment of the powdered substance characterizing parameters, which offer pertinent data about the material's appropriateness for direct compression (DC) of tablet, which involves mathematical modeling and Semisolid Control Diagram using software like iTCM. The SeDeM diagram expert system (DES) determines the suitability of excipients and active ingredients for DC and the ratio of API to excipient is calculated. The DC is most suitable as it saves time and makes process easy, but these technique excipients compensate for their poor flow. Thus, a new system was required to help reduce number of experiments and time for making an optimized direct compression tablet. The SeDeM DES is based on quality by design (QbD) (ICH Q8) as it evaluates critical quality attributes that affect finished product's quality. This review mainly focuses on various dosage forms like Solid, Semisolid, Liquisolid, and Solidified liquid dosage forms. These techniques mainly characterize all substances using 12 parameters, resulting 12-sided regular polygon. However, parameters may increase or decrease according to the requirement of a particular dosage form like an Orodispersible tablet 15 and a Semisolid dosage form applying 5 parameters. The rationales behind limits for indexes are justified accordingly.

Nose to brain delivery of nanosuspensions with first line antiviral agents is alternative treatment option to Neuro-AIDS treatment.

Intranasal drug delivery is one of the uprising areas of the research in targeting drug to the brain. Nose to brain drug delivery follows the olfactory pathway and purportedly known to be more efficient to deliver neuro-therapeutics to the brain by circumventing the BBB and thereby increasing bioavailability of drugs in the brain. The advantage of this method is non-invasiveness, rapid onset of action and helps to achieve site specific delivery. In this research work nanosuspension were prepared using combination of antiretroviral agents for Neuro-AIDS treatment. Nanosuspensions were prepared by high-speed homogenization, wet milling and high-pressure homogenization techniques. Formulations were analysed by SEM, FTIR, and DSC. Morphology and stability analysis was done by analysing zeta potential, particle size, and PDI. Ex-vivo diffusion study and histopathological analysis was performed using goat nasal mucosa. High pressure homogenization was found to be best technique for formulation of nanosuspension. Antiviral drugs could be delivered successfully by optimizing nasal dosage form.

Stability-indicating LC Method for Quantification of Azelnidipine: Synthesis and Characterization of Oxidative Degradation Product

Objectives: In the work presented here, the degradation behavior of azelnidipine under diverse forced degradation conditions was studied. A stability-indicating liquid chromatographic method was established which could separate and resolve azelnidipine from its degradation products. Further, chemical kinetics under acidic and alkaline conditions were studied, and validation studies were performed. Materials and Methods: Using reversed-phase chromatography, azelnidipine and its formed degradants were resolved using phosphate buffer (pH 3.0) and methanol in a mixture of 10:90% v/v as a mobile phase at a flow rate of 1.0 mL/min. All eluents were detected at a wavelength of 256 nm. Results: Azelnidipine was degraded under acid, alkali, wet heat, and oxidized environment. The pH-dependent rate of hydrolysis of azelnidipine was studied under acidic and alkaline conditions and chemical kinetics were determined. Further, the oxidative degradation product of azelnidipine was synthesized and characterized as 3-(1-benzhydrylazetidin-3-yl) 5-isopropyl 2-amino-6-methyl-4-(3-nitrophenyl) pyridine-3,5-dicarboxylate (dehydro-AZD). Conclusion: The susceptibility of azelnidipine to hydrolysis was attributed to the presence of ester at 3 and 5 positions of 1,4 dihydropyridine. Further, under oxidative conditions, the aromatization of 1,4 dihydropyrinine resulted in dehydro-AZD. Azelnidipine followed the first-order reaction under acid and alkali hydrolysis, and was more susceptible to degradation under acidic conditions. The synthesized and confirmed dehydro-AZD was found as one of the metabolites and impurities of azelnidipine. The evaluated validation parameters ascertained the practicality of the method for the quantification of azelnidipine tablets.

Formulation of PPAR-gamma agonist as surface modified PLGA nanoparticles for non-invasive treatment of diabetic retinopathy: in vitro and in vivo evidences.

Diabetic retinopathy is one of the worst complications of diabetes and it is treated by invasive method. We prepared a surface modified poly (D, L-lactide-co-glycolide) i.e. PLGA nanoparticles for delivery of pioglitazone-a peroxisome proliferator-activated receptor-gamma agonist to posterior segment of the eye by topical administration. The present study investigated two grades of PLGA viz. 75:25 and 50:50. Surface modification was performed using polysorbate 80. Nanoparticles were prepared by single emulsion solvent evaporation method and optimized by using 3-factor 3-level Box-Behnken statistical design. Mean particle size, PDI and entrapment efficiency for optimized batch of PLGA 75:25 was found to be 163.23 nm, 0.286 and 91%, whereas; for PLGA 50:50 it was 171.7 nm, 0.280 and 93% respectively. DSC confirms the molecular dispersion of drug in polymer. In vitro release study showed biphasic drug release pattern with 58.48 ± 1.38% and 74.17 ± 1.38% cumulative drug release by PLGA 75:25 and 50:50 nanoparticles at the end of 10h. The release profile of pioglitazone from nanoparticles appeared to fit best with Higuchi model. In vivo study on rat showed dose dependent reduction in vascular endothelial growth factor concentration in vitreous fluid. The study reveals significance of peroxisome proliferator-activated receptor-gamma in management of diabetic retinopathy.

Design, synthesis and molecular modeling studies of few chalcone analogues of benzimidazole for epidermal growth factor receptor inhibitor in search of useful anticancer agent.

In the present investigation, few 3-(substitutedphenyl)-1-[2-(1-hydroxy-ethyl)]-1H-benzimidazol-1-yl)prop-2-en-1-ones are EGFR antagonist are designed, by molecular docking analysis. The synthesized compounds were tested for their in vitro anticancer activity by propidium iodide fluorescent assay and Trypan blue viability assay against colorectal cancer cell lines (HCT116) and non-small cell lung cancer cell lines (H460). Human Epithelial Kidney cell lines (HEK) are used as normal cell lines for studying effect of drug on non-cancerous cells within human body. Evaluation of cytotoxic studies of synthesized compounds CHL(1-8) reveal that compound CHL1 [IC50=7.31 and 10.16 µM against HCT116 and H460 cell lines respectively, by PI assay] and CHL8 [IC50=12.52 and 6.83 against HCT116 and H460µM cell lines respectively] possess promising cytotoxic activity.

Formulation and development of plasma volume expander using natural and modified starch from Solanum tuberosum.

BACKGROUND: To formulation and development of plasma volume expander (PVE) by using natural and modified starch from Solanum tuberosum. The function of blood circulation is to provide the needs of the body tissues and to maintain an appropriate environment in all tissue fluids of the body for the optimal survival and functions of the cells. Rapid restoration of the blood volume is necessary to decrease reduction in the amount of the blood. The PVEs are isotonic colloidal solutions, act by increasing the osmotic pressure of the intravascular compartment, which leads to the influx of the interstitial fluids through the capillary pore which, in turn, leads to the increase in the volume of the blood. Therefore, there is a need to discover the PVE with less side effects. The main aim of the present study is to use amylopectin as PVEs, fractionated from natural and modified starch obtained from S. tuberosum. METHODS: The starch extracted from the normal grains and the tubers of potatoes was selected for the production of starch. Statistical analysis includes in vitro characterization that involves viscosity studies, plasma-product interaction, osmotic pressure detection, molecular weight-viscosity relationship, determination of weight average molecular weight, enzymatic interaction, and in vivo characterization such as toxicity studies and the effect of the products on the blood coagulation. The isolated starch and fractionated amylopectin were analyzed for the physicochemical characteristics. RESULT AND CONCLUSION: The amylopectin fractionated from isolated starch from grains and tubers of potatoes can be used as PVE, as per the outcome of the study.

Formulation of mucoadhesive gastric retentive drug delivery using thiolated xyloglucan.

Tamarind seed xyloglucan is a polymer reported to possess mucoadhesive property. In the present work, role of cysteine derivative of tamarind seed polysaccharide (thiomer) to enhance the mucoadhesion and its influence on drug permeation has been studied. The xyloglucan was first chemically modified to carboxymethyl derivative which was further converted to thiomer by conjugation with cysteine in presence of a coupling agent, EDAC. The matrix tablets of simvastatin prepared using thiomer demonstrated drug release retardation, increased mucoadhesion force and increased ex vivo permeation, the same were proportional to the increase in the amount of thiomer. The in vivo residence of thiomer placebo was more than 7h in rabbit. Pharmacokinetic evaluation in rabbits indicated higher AUC for the formulation with highest content of thiomer and level 'A' correlation could be established from the generated dissolution and bioavailability data.

Design and development of SMEDDS for colon-specific drug delivery.

CONTEXT: Lipoidal systems have particularly shown potential for specific accumulation in areas with inflamed tissue increasing the selectivity of local drug delivery. OBJECTIVE: Formulation and evaluation of self-microemulsifying drug delivery system (SMEDDS) for colon-specific drug delivery for effective treatment of colonic diseases. METHOD: Ternary phase diagram was used to optimize level of oil, surfactant and co-surfactant to optimize SMEDDS and were evaluated for percent transmittance, emulsification time, in vitro release, myeloperoxidase (MPO) activity and intestinal accumulation. The spray dried SMEDDS were filled in capsules which were enteric coated with Eudragit S-100 at 10% weight gain to ensure SMEDDS delivery at colon. The spray dried SMEDDS were also evaluated for IR, DSC, XRD, SEM and stability study. RESULT: In ternary phase diagram, Capmul MCM C8 and Capmul PG12 NF with surfactant (Tween 20) and co-surfactant (PG) in ratio 2:1 and 3:1, respectively, showed maximum emulsification area. These liquid SMEDDS show maximum transmittance, globule size of 90-30 nm. The spray-dried SMEDDS with diluents show good flow property. The units of MPO activity show lower level as compared to pure drug and control group, histopathology results supports better healing with SMEDDS. This was attributed to accumulation of SMEDDS in inflammatory area as compared to drug which was further proved by accumulation study. Enteric-coated capsule containing SMEDDS are able to deliver drug, specifically at the colonic region. CONCLUSION: Higher accumulation of lipoidal drug in inflammatory area and specific release of liposomes by enteric-coated capsules provide better option for the treatment of colonic disease.

In-vivo bioavailability and lymphatic uptake evaluation of lipid nanoparticulates of darunavir.

Darunavir is effective against wild-type and PI-resistant HIV, and has an oral bioavailability of 37%. It needs to be combined with ritonavir, which increases the bioavailability to 82%. The aim of this study was to evaluate the in-vivo efficacy of the darunavir-SLN and demonstrate lymphatic transport as a contributing pathway in increasing the drug bioavailability. The SLN was prepared by hot-homogenization technique using GMS as lipid. In-vitro drug release from SLN at the 12th hour was retarded (80.6%) compared to marketed tablet (92.6%). Ex-vivo apparent permeability of the freeze-dried SLN across everted rat intestine was 24 × 10-6 at 37 °C and 5.6 × 10-6 at 4 °C. The presence of endocytic process inhibitors like chlorpromazine and nystatin reduced it to 18.8 × 10-6 and 20.2 × 10-6, respectively, which established involvement of endocytic mechanism in the uptake of SLN. In-vivo pharmacokinetic studies on rats demonstrated increase in the AUC of SLN (26) as compared to that of marketed tablet (13.22), while the presence of lymphatic uptake inhibitor cycloheximide lowered the AUC of SLN to 17.19 which further led credence to the involvement of lymphatic uptake behind improved bioavailability. The detection of darunavir in the lymphatic fluid of the rats administered with darunavir-SLN further reinforced the conclusion of SLN being taken up by the lymphatic system.

Design and development of liposomes for colon targeted drug delivery.

BACKGROUND: Local delivery to bowel tissue through oral administration is a challenging but a desirable goal to treat diseases like inflammatory bowel disease (IBD). Colon specific drug delivery system should be capable of protecting the drug en route colon. PURPOSE: Liposomes have shown potential to specific accumulation at inflammation site thus reduce toxicity; hence it can be used for effective treatment of IBD. METHODS: Liposomes prepared using thin film hydration method. Statistical design was used for optimization. Colitis was induced using acetic acid. Inverted sac method was used as ex vivo model for IBD. Myeloperoxidase (MPO) activity and histopathology comparative study was carried out. Liposomes were formulated in enteric coated capsules to deliver the liposome specifically in initial segment of colon. RESULTS: Particle size and entrapment efficiency were between 200 and 300 nm and 40 and 60%, respectively. In vivo and ex vivo study indicates higher accumulation of liposomes in colonic region as compared to pure drug. Enteric coated capsules delivered the drug after 5 h lag time. DISCUSSION: Low particle size is attributed to low lipid content and stabilization due to surfactant. At higher cholesterol level, vesicles cannot reshuffle into smaller vesicles due to rigidization. Study shows higher accumulation of liposomes due to its lipoidal nature as compared to pure drug due to membrane transfer mechanism of drug thus MPO significantly lowers as compared to standard group (p < 0.05). CONCLUSIONS: Higher accumulation of liposomal drug in inflammatory area and specific release of liposomes by enteric coated capsules provide better option for the treatment of colonic disease.

Development and evaluation of carvedilol-loaded transdermal drug delivery system: In-vitro and in-vivo characterization study.

CONTEXT: The transdermal drug delivery system was prepared and the bioavailability of the selected drug was enhanced by reducing first-pass metabolism. OBJECTIVE: The objective of this study was to enhance the bioavailability of carvedilol through transdermal patches. MATERIALS AND METHODS: To develop a matrix-type transdermal patch containing carvedilol with different ratios of polymer combinations by solvent evaporation technique. RESULTS AND DISCUSSION: In-vitro permeation studies were performed by Franz diffusion cells. The results followed Higuchi kinetics, and mechanism of release was diffusion mediated. On the basis of the in-vitro and physicochemical parameters of carvedilol patches, the code F-1(PVP: Ethyl Cellulose = 4:1) was chosen for the study of in-vivo, ex-vivo, histocompatibility study, and pharmacological study. The bioavailability studies in rats indicated that the carvedilol-loaded transdermal patches provided steady-state plasma concentration and improved bioavailability of 72% in comparison to oral administration. The ex-vivo permeation study in rat's skin indicated that the flux and permeability co-efficient of optimized F-1 patch was 30.08 ± 0.7 µg/cm(2)/h and 0.416 ± 0.05 µg/cm(2)/h, respectively, which was more as compared to plain carvedilol. The histocompatibility study of the F-1 patch on the rat's skin after 24 h ex-vivo study gave less pathological changes as compared to other. The antihypertensive activity of the patch in comparison with oral administration was studied using N-nitro-L-arginine methyl ester-induced hypertensive rats. It was observed that the optimized patch (F-1) significantly controlled hypertension (p < 0.05). CONCLUSION: The developed patch increases the efficacy of carvedilol through enhancement of bioavailability for the therapy of hypertension.

Preparation and characterization of nanocapsules for colon-targeted drug delivery system.

CONTEXT: Nanoparticles for colon-specific drug delivery system are known for their specific accumulation in the inflamed tissue in the colon and may therefore allow a selective delivery to the site of inflammation for the treatment of inflammatory bowel disease (IBD). OBJECTIVE: The objective of this study was to formulate and evaluate nanocapsules (NC), an oral system designed to achieve site-specific and instant drug release in colon for effective treatment of IBD. MATERIALS AND METHODS: Prednisolone (PD), a typical glucocorticoid, has been widely used for the treatment of IBD. In this study, nanoprecipitation method was used to prepare polymeric NC of PD with pH responsive polymer Eudragit S100. The effect of several formulation variables such as surfactant, oil, and polymer on the PD-NC properties (average size, drug release rate, and drug entrapment) was investigated. In vitro drug release study was done by changing pH method and an in vivo study on rat was done to ascertain efficiency of PD-NC to release drug specifically in colon. RESULTS AND DISCUSSION: The optimized formulations lead to the preparation of PD-NC with a mean size of 567.87 nm, high encapsulation efficiency of 90.21%. In vitro studies reveal that NC releases the drug after 4.5-h lag time corresponding to time to reach colonic region, and in vivo studies show that NC release drug after 3-h lag time in rat corresponds to arrival in colon. CONCLUSION: The above NC formulation of PD is the targeted drug to the colon and may provide effective way of treatment of colonic disease.

Statistical optimization of floating pulsatile drug delivery system for chronotherapy of hypertension.

INTRODUCTION: A pulsatile drug delivery system is characterized by a lag time that is an interval of no drug release followed by rapid drug release. The purpose of this work was to develop hollow calcium alginate beads for floating pulsatile release of valsartan intended for chronopharmacotherapy. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. MATERIALS AND METHODS: To overcome the limitations of various approaches for imparting buoyancy, hollow/porous beads were prepared by simple process of acid-base reaction during ionotropic crosslinking by low viscosity sodium alginate and calcium chloride as a crosslinking agent. In this study, investigation of the functionality of the sodium alginate to predict lag time and drug release was statistically analyzed using the response surface methodology (RSM). RSM was employed for designing of the experiment, generation of mathematical models and optimization study. The chosen independent variables, i.e. sodium alginate and potassium bicarbonate were optimized with a 3(2) full factorial design. Floating time and cumulative percentage drug release in 6 h were selected as responses. RESULTS: Results revealed that both the independent variables are significant factors affecting drug release profile. A second-order polynomial equation fitted to the data was used to predict the responses in the optimal region. The optimized formulation prepared according to computer-determined levels provided a release profile, which was close to the predicted values. The floating beads obtained were porous (21-28% porosity), hollow with bulk density <1 and had Ft(70) of 2-11 h. The floating beads provided expected two-phase release pattern with initial lag time during floating in acidic medium followed by rapid pulse release in phosphate buffer. CONCLUSION: The proposed mathematical model is found to be robust and accurate for optimization of time-lagged formulations for programmable pulsatile release of valsartan.

Design, development and in vitro-in vivo study of a colon-specific fast disintegrating tablet.

OBJECTIVE: Targeted delivery systems for the treatment of Inflammatory bowel disease (IBD) are designed to increase local tissue concentrations of anti-inflammatory drugs from lower doses compared with systemic administration. The objective of this study was to formulate and evaluate an oral system designed to achieve site-specific and instant drug release in the colon for effective treatment of IBD. MATERIALS AND METHODS: The system consists of a core tablet containing the model drug diclofenac sodium, superdisintegrant sodium starch glycolate, and coated with enteric polymer Eudragit FS 30 D to achieve different total percentage weight gain. Drug release studies were carried out using a changing pH method. A placebo formulation containing barium sulphate in the tablet was administered to human volunteers for in vivo X-ray studies. SEM studies were performed to determine coating thickness and film topography. RESULTS: In vitro studies revealed that the tablet with 10% coating level released the drug after 5 h lag time corresponding to the colonic region. Tablets with 10% coating level could maintain their integrity in human volunteers for 5 h, approximating colon arrival time and release the drug instantaneously. DISCUSSION: Colon-targeting and instant drug release for 10% coating level was due to the dissolution of the Eudragit FS 30 D and the immediate release effect of superdisintegrant. It was observed that as the coating level increased, the lag time also increased. This was because of increased diffusion path length and tortuosity at higher coating levels. CONCLUSION: An in vivo-in vitro study revealed that not only the sensitivity of the polymer to the pH environment but also the thickness of coating plays an important role in colon delivery and the tablet with 5% superdisintegrant and 10% coating level achieved the desired performance of the colon targeting.