Sustained-release Granules Research Articles

The Preparation and In-vitro Evaluation of Sustained Release Capsules of Rivastigmine Tartrate

Rivastigmine tartrate is a cholinesterase inhibitor, used in the treatment of dementia associated with Parkinson’s disease and it is currently available in a capsule form. Hydroxy Propyl Methyl Cellulose (HPMC) is the most important hydrophilic carrier material used for the preparation of oral controlled drug delivery systems due to its high swellability and its significant effect on the release kinetics of an incorporated drug. The present study was designed to prepare sustained release granules of Rivastigmine tartrate by using HPMC as matrix former, Microcrystalline cellulose (MCC) as diluent and Magnesium Stearate as lubricant. Blend of Eudragit co-polymers on different ratio was used to coat the granules. The drug-excipient compatibility studies were carried out by using FT-IR, DSC and XRPD analysis. The results shown that there was no significant interaction between the drug and excipients. Granules were prepared by wet granulation method. The granules were subjected to physico-chemical, drug content and in-vitro drug release studies. The best fit release kinetics was achieved with Higuchi equations followed by first order kinetics from the above results it was concluded that extended release granules of Rivastigmine tartrate can be prepared by using HPMC and also found that coating of granules with Eudragit co-polymers also effective to extend the release of drug.

Florfenicol sustained-release granules: an in vitro-in vivo correlation study in pigs

The objective of this study was to synthesize and characterize pharmaceutical characteristics of florfenicol sustained-release granules (FSRGs) in vitro and in vivo. FSRGs were synthesized using monostearate, polyethylene glycol 4000 and starch. In vitro dissolution profiles were studied using the rotating basket method in pH 1.2 HCl solution and pH 4.3 acetate buffer. Twenty-four male healthy Landrace×Yorkshire pigs were equally divided into three groups and administered a 20 mg/kg i.v bolus of florfenicol solution and dosed orally with FSRGs in the fasting and fed states. The Higuchi model was the best fit for the drug release profile in pH 1.2 and pH 4.3 media, and the mechanism of drug dissolution was governed by both diffusion and dissolution. We established a level A in vitro - in vivo correlation for FSRGs and the in vivo profile of the FSRGs can be estimated by the in vitro drug release.

Mechanistic insight into the inhibitory effect of artemisinin sustained-release inhibitors with different particle sizes on Microcystis aeruginosa.

Environment-friendly algaecides based on allelopathy have been widely used to control harmful algal blooms. In this research, micro and nano scale artemisinin sustained-release algal inhibitor was prepared, the optimal preparation conditions were explored, and the inhibitory mechanism of artemisinin algaecides was turned perfect. The results showed that when the particle size of artemisinin sustained-release microspheres (ASMs) was 2/10,000 of artemisinin sustained-release granules (ASGs), the inhibitory effect was more remarkable. The optimal concentration of ASMs was 0.2gL-1, and the inhibitory effect reached 99% on the 10th day. The algal density and chlorophyll a both showed a downward trend, indicating that ASGs and ASMs could promote the degradation of chlorophyll a. The inhibition rate of ASGs was faster than that of ASMs on the 4th day, and the inhibitory effect of ASMs was more significant after the 5th day. The activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) increased rapidly at first and then decreased, which indicated that ASGs and ASMs caused oxidative damage to Microcystis aeruginosa and inhibited the activity of antioxidant enzymes. Furthermore, the content of the oxygen free radical (O2-) and malondialdehyde (MDA) continued to rise after the 5th day, and the protein, nucleic acid, and conductivity in the culture medium increased. These results showed that lipid peroxidation occurred in the algal cell membrane, and the permeability of the membrane increased. In summary, the ASMs had a significant sustained inhibitory effect while the ASGs had a better short-term effect. The main inhibitory mechanism of artemisinin algaecides is the irreversible damage of cell membrane.

Efficacy of Wumei Baijiang prescription on regulatory T cells / helper T cells Immune balance in mice with ulcerative coliti.

To observe the therapeutic effect of Wumei Baijiang prescription empirical prescription of Lu Zhizheng, on experimental ulcerative colitis (UC) mice, and to investigate the mechanism of the prescription in UC from the perspective of the immune balance of regulatory T cells (Treg) and helper T cells (Th17). Sixty C57BL/6 mice were randomly divided into 6 groups: normal group, model group, Chinese medicine group (high, medium and low dose group of Wumei Baijiang prescription) and control group (mesalazine sustained-release granules). Except for the normal group, the other groups used 2.5% dextran sulfate sodium to induce UC mice model. At the end of the model, the Chinese medicine group was given high, medium and low dose administration of Wumei Baijiang prescription, the control group was given slow-release granules of mesalazine, and the model group was given equal volume saline for 10 d. The changes of food intake, body weight, disease activity index (DAI) score, length of large intestine and histopathology were observed. The number of Treg, Th17, CD4+, CD8+ cells in spleen was detected by flow cytometry. The expression of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and C-reactive protein (CRP) in serum was detected by enzyme-linked immunosorbent assay. The middle and high-dose groups of Wumei Baijiang prescription were superior to the model group in terms of increasing food intake and body weight of colitis mice, restoring colon morphology, improving pathological damage, and reducing DAI (P < 0.05). There was no statistical difference with the mesalazine group (P > 0.05). Compared with the model group, the spleen Treg and CD4+ of the mice in the high and middle dose groups of Wumei Baijiang prescription were higher, while Th17 and CD8+ were lower (P < 0.05), and there was no statistical difference compared with the mesalazine group (P > 0.05). In addition, compared with the model group, the serum levels of TNF- and CRP in mice with high and middle doses of Wumei Baijiang prescription and mesalazine group were lower (P < 0.05), and IL-10 content was higher ( P < 0.05). Wumei Baijiang prescription can improve the general conditions of colitis mice, such as diarrhea, hematochezia, weight loss, and mucosal damage. The mechanism may be related to the regulation of Treg/Th17 immune balance.

Anti-inflammatory effect of Sustained release granules of Aceclofenac in Gouty Arthritis Rat

Gout is most common painful clinical syndrome occurs due to hyperuricaemia (high serum uric acid level) and deposition of monosodium urate crystals in joints. In the current experimental study, the anti-inflammatory effect of sustained release granules of aceclofenac, was investigated on monosodium urate crystal-induced inflammation in rat. Monosodium urate is injected appropriately at a dose of 3 mg/kg body weight of a rat on right ankle to induce inflammation in joint like gouty arthritis. The percentage of joint swelling in positive control group was increased significantly (p&lt;0.5) when compared with normal group after 1 hr, 12 hr and 24 hr with a single injection of MSU. Therapeutic effect of sustained released granules (OD) is similar to conventional released granules (BD) and possesses an anti-inflammatory effect, which could provide relief in gouty arthritis after administration of sustained release formulation of aceclofenac once in a day only. The current study clearly indicated that slow release granules of aceclofenac exerted a strong anti-inflammatory effect against gouty arthritis at standard dose once daily. It concluded that, when aceclofenac tablet is formulated with slow release granules it decreases the dosing frequency with same therapeutic effect.

Stress of Artemisinin Sustained-Release Granules on Photosystem II, Reactive Oxygen Species and Metabolic Activity of Microcystis aeruginosa Cells.

The inhibitory mechanisms of artemisinin anti-algae sustained-release granules (AASG) on algal cells at cytoplasmic level were investigated. The results showed that 0.2g L-1 AASG could effectively inhibit the growth of Microcystis aeruginosa (M.aeruginosa). The stress of 0.2g L-1 AASG changed the excitation energy distribution pattern of Photosystem II (PSII) of algal cells, which showed the increase of heat dissipation share and the inhibition of physiological activities related to PSII. At the same time, AASG induced a large amount of reactive oxygen species (ROS), which aggravated the membrane lipid peroxidation and caused serious damage to algae cell membrane. AASG also resulted in the decrease of esterase activity and alkaline phosphatase activity (APA) in algal cells. Results showed that AASG inhibited algal growth by exerting adverse effects on PSII, ROS and metabolic activity of M.aeruginosa.

Study of Production of Fine Globular Granules for Oral Solid Dosage Form in the Unique Multi-functional Rotor Processor

In pharmaceutical field, technology for manufacturing fine globular granules with a narrow size of particle distribution (100–200 μm) are crucially important in enhancing patient adherence and controlling drug release from functional granules, e.g., sustained release or taste-masking granules. A unique multi-functional rotor processor, “Granurex®” (GX, Freund, Japan), facilitate manufacturing the fine globular granules. In this study, we examined the relationships between operational conditions of the multi-functional rotor processor and the physical characteristics of the obtained granules, and optimized the manufacturing conditions for producing fine globular granules. In addition, we developed highly drug-loaded fine globular granules which composed of almost drug substance (>97%). We believe fundamental information obtained in this study will be important for the development of processes for the facile manufacture of fine globular granules of various drugs.

Toxic response of aquatic organisms to guide application of artemisinin sustained-release granule algaecide

In our previous study, we prepared the granules by embedding artemisinin into alginate-chitosan using microcapsule technology. These granules can release artemisinin sustainably and have a strong inhibitory effect on the growth of both single Microcystis aeruginosa and mixed algae. To safely and effectively use artemisinin sustained-release granules to control algal blooms, the ecotoxicity was studied by assessing their acute and chronic toxicity to Daphnia magna (D. magna) and Danio rerio (D. rerio), along with their antioxidant activities. The results showed that the 48-h median effective concentration (EC50) of pure artemisinin to D. magna was 24.54 mg/L and the 96-h median lethal concentration (LC50) of pure artemisinin to D. rerio was 68.08 mg/L. Both values were classified as intermediate toxicity according to the Organization for Economic Co-operation and Development (OECD). The optimal algae inhibitory concentration of artemisinin sustained-release granules (1 g/L) had low acute toxicity to both D. magna and D. rerio. The sustained-release granules had higher chronic toxicity to D. magna than to D. rerio. Partial indices of D. magna were inhibited by granules when the concentrations were larger than 0.1 g/L. Low granule concentration had an inductive effect on antioxidant enzyme activities in D. magna and D. rerio. With the increase of the exposure concentration and time, the enzyme activity presented a trend of first increasing and then decreasing, and the overall changes were significant. The change trend and range of enzyme activity indicated that the granules could cause serious oxidative stress to D. magna and D. rerio, and the changes were consistent with the results of toxicity experimentation.

Preparation, optimization and in vitro\u2013in vivo evaluation of Shunxin sustained release granules

BackgroundShunxinzufang decoction is tutors, empirical formula and has been used in Chinese patients of HFpEF for several years. The aim of this study was to make into sustained release granules and select the best formula for the preparation of Shunxin sustained release granules and to evaluate its in vivo and in vitro drug release behavior.MethodsResponse surface methodology and Center composite design were applied to screen the optimal formula of Shunxin sustained release granules. HPLC was used to detect indicative ingredients—paeoniflorin, calycosin-7-glucoside and ferulic acid in Shunxin sustained release granules. The in vitro sustained release character of indicative ingredients was investigated in simulated digestive fluids. In-vivo process of active components was studied through pharmacokinetics.ResultsThe optimal formula of Shunxin sustained release granules consisted of 35% shunxinzufang extract and 65% HPMC/starch (HPMC/starch ratio = 2:1). Three indicative components can be separated well under selected HPLC conditions. Compared with Shunxinzufang extract, the active components of Shunxin sustained release granules have obvious sustained-release character and improved bioavailability.ConclusionShunxin sustained release granules has obvious sustained-release character and improved bioavailability.

Clinical study of Yiqi-Jiedu decoction combined with mesalazine sustained release granules for the patients with ulcerative colitis

Objective To evaluate the effect of Yiqi-Jiedu decoction combined with mesalazine sustained release granules for the patients with ulcerative colitis (UC). Methods A total of 93 UC patients who met the inclusion criteria were divided into control group (46 cases) and study group (47 cases) according to the random number table method. The control group was treated with mesalazine sustained release granules orally. The treatment group added Yiqi-Jiedu decoction on the basis of the control group. Both groups were treated for 2 months. The level of plasma thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (6-Keto-PGF1α) and serum CRP, IL-1 and TNF-α were measured by ELISA, and the clinical effect was evaluated. Results The total effective rate was 95.7% (45/47) in the treatment group and 78.3% (36/46) in the control group. There was significant difference between the two groups (χ2=6.323, P=0.012). After treatment, the plasma TXB2 level in the treatment group was significantly lower than that in the control group (601.14 ± 13.31 pg/ml vs. 780.33 ± 16.54 pg/ml; t=57.619, P<0.01), and the plasma 6-Keto-PGF1α level was significantly higher than that in the control group (84.04 ± 11.39 pg/ml vs. 69.48 ± 10.21 pg/ml; t=6.487, P<0.01). After treatment, the level of CRP, IL-1 and TNF-α in the treatment group was significantly lower than those in the control group (t=15.457, 7.006 and 17.434, respectively, all Ps<0.01). Conclusions The Yiqi-Jiedu decoction combined with mesalazine sustained release granules can reduce the level of serum inflammatory cytokines in UC patients, reduce the level of plasma TXB2, and increase the level of plasma 6-Keto-PGF1α, so as to improve the clinical effectiveness. Key words: Colitis, ulcerative; Yiqi-Jiedu decoction; Inflammation; Therapies, investigational

Preparing of aspirin sustained-release granules by hot-melt granulation and micro-crystal coating

In this work, aspirin (ASP) sustained granules were prepared using micro-crystal coating and hot-melt granulation, respectively. In the process of micro-crystal coating, PVP was used to form the isolation layer and then coated with either Eudragit RS/RL30D or ethyl cellulose (EC) as sustained-release layers to prepare sustained granules (the granules from this method were denoted m-cG). And in the process of hot-melt granulation, the granules were obtained with stearyl alcohol as a binder and EC as matrix material to prepare sustained granules (the granules were denoted h-mG). The in vitro release of ASP sustained-release granules was investigated by dissolution apparatus and the stability of the granules was studied. Since both methods effectively prevented the hydrolysis of ASP, the sustained granules by micro-crystal coating and hot-melt granulation were stable. However, there was a clear difference in the in vitro release of h-mG and m-cG. The h-mG was completely released in 4 h, while the m-cG with EC as sustained-release layer released 80% in 24 h and the m-cG with the Eudragit RS/RL 30 D as sustained-release layer released completely in 5 h. The results showed that micro-crystal coating was more suitable for the preparation of ASP sustained granules, and the granules with EC as sustained layer could achieve a better sustained-release effect.

A population pharmacokinetic model taking into account protein binding for the sustained-release granule formulation of valproic acid in children with epilepsy

The objective of this work was to develop a population pharmacokinetic model for a prolonged-release granule formulation of valproic acid (VPA) in children with epilepsy and to determine the doses providing a VPA trough concentration (Ctrough) within the target range (50-100mg/L). Ninety-eight children (1-17.6years, 325 plasma samples) were included in the study. The model was built with NONMEM 7.3. The probability to obtain Ctrough between 50 and 100mg/L was determined by the Monte Carlo simulations for doses of 20, 30, 40, and 60mg/kg/day and body weights between 10 and 70kg. A one compartment model, with first-order absorption and flip-flop parameterization and linear elimination, but taking protein binding into account, was used to describe the data. Typical values for unbound VPA clearance and distribution volume were 6.24L/h/70kg and 130L/h/70kg respectively. Both parameters were related to body weight via allometric models. The highest probability to obtain a Ctrough within the target range for 10-kg children was obtained with a 40mg/kg daily dose, whereas daily doses of 30 and 20mg/kg were found appropriate for 20 to 30- and ≥ 40-kg children respectively. However, for these same doses, the exposure to unbound VPA could differ by 40%. If the present study supports the current dose recommendations of 20-30mg/kg/day, except for children under 20kg, who may need higher doses, it also highlights the need for further research on the pharmacokinetics/pharmacodynamic profile of unbound VPA.

Some Variables Affecting the Formulation of Pentoxifylline (PTX) as a Solid Sustained Release Dosage Form

An inert matrix that is used to control the release of (PTX) was prepared using Eudragit RL100 and RSPM types as matrix forming agent . The matrices were prepared by either dry granulation(slugging) , or wet granulation method using chloroform as a solvent evaporation vehichle. The cumulative release was adjusted by using polyvinylpyrollidone (PVP) or ethylcellulose (EC) polymers .The results indicated that both methods of preparation were valid for incorporation PTX as a sustained release granules .Moreover ,the results revealed that best polymer used was Eudragit RSPM in 3:20 polymer drug ratio .Besides to that , the results indicated that the release profiles were affected by pH- medium , PVP and EC addition as an enhancer or retardant polymer used respectively. As well as to the method of preparation .&#x0D; Key words : Pentoxifylline Sustained Retease , Eudragit RS , RL .

Design and Evaluation of Novel Oro-Dispersible Sustained Release Tablets of Poly Ethylene Glycol based Solid Dispersion of Domperidone

Solid dispersion has been widely used as cost efficient solubility enhancement technique for poorly water-soluble drugs. Domperidone (DOM) is practically insoluble in water which resulted in its poor oral bioavailability. Solid dispersion of DOM with poly ethylene glycol 4000 (PEG) in 1:3 was prepared by melting method to improve solubility of DOM. Solid dispersions were characterized by FTIR, DSC and XRD techniques. Further solid dispersion of DOM was treated with molten lipid to form solid dispersion based sustained release (SDSR) granules. The integrity of solid dispersion in SDSR granules was also investigated by XRD studies. Drug release from SDSR granules was sustained up to 12 hrs. Finally, orodispersible (OD-SDSR) tablet of SDSR granules were prepared in order to improve patient compliance. The optimum formulation was rapidly disintegrated within 40 seconds.

Effects of artemisinin sustained-release granules on mixed alga growth and microcystins production and release.

To safely and effectively apply artemisinin sustained-release granules to control and prevent algal water-blooms, the effects of artemisinin and its sustained-release granules on freshwater alga (Scenedesmus obliquus (S. obliquus) and Microcystis aeruginosa (M. aeruginosa)), as well as the production and release of microcystins (MCs) were studied. The results showed that artemisinin sustained-release granules inhibited the growth of M. aeruginosa (above 95% IR) and S. obliquus (about 90% IR), with M. aeruginosa more sensitive. The artemisinin sustained-release granules had a longer inhibition effect on growth of pure algae and algal coexistence than direct artemisinin dosing. The artemisinin sustained-release granules could decrease the production and release of algal toxins due to the continued stress of artemisinin released from artemisinin sustained-release granules. There was no increase in the total amount of MC-LR in the algal cell culture medium.

Mesalazine sustained-release granules taking once daily or multi-times daily in the treatment of mild to moderate active ulcerative colitis: a randomised controlled clinical trial

Objective To investigate the efficacy, safety and compliance of mesalazine sustained-release (SR) granules taking once daily or multi-times daily in the treatment of patients with mild to moderate active ulcerative colitis. Methods Sixty patients with mild to moderate active ulcerative colitis were divided into group A, B and C with 20 patients in each group. Group A received mesalazine SR granules 4 g once daily, Group B with 2 g each time and twice daily, Group C with 1 g each time and four times daily. The total course was eight weeks. The vital signs, Mayo score, compliance and adverse effects of patients were monitored at 0, 4th, 8th weeks.At 0 and 8th weeks, colonoscopy were performed. The parameters of efficacy assessment were clinical complete remission rate, clinical remission rate, efficacy rate, mucosal healing rate, remission time and safety. The F test, t test or Chi-square test was performed for comparison among groups. Results The clinical complete remission rate of group A, B and C was 20%(4/20), 10%(2/20) and 10%(2/20), respectively. The clinical complete remission rate was 70%(14/20), 65%(13/20) and 70%(14/20), respectively. The efficacy rate was 95%(19/20), 85%(17/20) and 90%(18/20), respectively. The mucosal healing rate was 70%(14/20), 60%(12/20) and 50%(10/20), respectively. The side effects rate was 20%(4/20), 15%(3/20) and 20%(4/20). There was no significant difference between groups (all P>0.05). The remission time of group A and B was (15.4±3.7) days and (15.6±2.9) days, which were both shorter than that of group C (18.4±3.6) days, and the differences were statistically significant (t=2.661 and 2.710, both P<0.05). There was no significant difference among three groups in gender, disease course, severity, location and clinical remission rate of sub-groups. Conclusions The efficacy and safety of mesalazine SR granules taking once daily or multi-times daily are similar in the treatment of patients with mild to moderate active ulcerative colitis. Once daily have better compliance than other regimens. Key words: Colitis, ulcerative; Mesalazine sustained-release granules; Once-daily; Efficacy; Safety

Pediatric drug formulation of sodium benzoate extended-release granules

Urea cycle disorders are a group of inherited orphan diseases leading to hyperammonemia. Current therapeutic strategy includes high doses of sodium benzoate leading to three or four oral intakes per day. As this drug is currently available in capsules or in solution, children are either unable to swallow the capsule or reluctant to take the drug due to its strong bitter taste. The objective of the present study was to develop solid, multiparticulate formulations of sodium benzoate, which are suitable for pediatric patients (i.e. flavor-masked, easy to swallow and with a dosing system). Drug layering and coating in a fluidized bed were applied for preparing sustained-release granules. Two types of inert cores (GalenIQ® and Suglets®) and three different polymers (Kollicoat®, Aquacoat® and Eudragit®) were tested in order to select the most appropriate polymer and starter core for our purpose. Physical characteristics and drug release profiles of the pellets were evaluated. A Suglets® core associated with a Kollicoat® coating seems to be the best combination for an extended release of sodium benzoate. A curing period of 8 h was necessary to complete film formation and the resulting drug release pattern was found to be dependant of the acidity of the release medium.

Design and characterization of cefuroxime axetil biphasic floating minitablets

Biphasic floating minitablets of cefuroxime axetil were prepared by melt granulation technique using two different grades of gelucire namely 50/13 and 43/01 to maintain constant plasma drug concentration. Loading dose of cefuroxime axetil was formulated as immediate release (IR) minitablets by using hydrophilic grade of gelucire 50/13. Maintenance dose was formulated as floating sustained release (SR) minitablets by using hydrophobic grade of gelucire 43/01. The prepared IR and SR granules were subjected to micromeritic studies and scanning electron microscopy. Fourier transform infrared spectroscopy (FT-IR) study revealed that drug and selected carriers were compatible. In vitro dissolution study of optimized IR minitablets showed more than 85% of loading dose dissolved within 30 min. Optimized SR minitablets showed zero lag time with floating duration more than 12 h. The drug release from SR minitablets was linear with square root of time with non-Fickian diffusion-controlled release. The optimized batch of minitablets was filled into 0 size hard gelatin capsule. In vitro dissolution study for capsule showed an immediate burst release followed by SR up to 12 h. There is no significant change in dissolution data after storage at 40 °C and 75% RH for three months. Microbiological assay of dissolution samples of optimized minitablets filled in capsules showed proportionate increase in inhibition of growth against Escherichia coli up to 12 h samples. In vivo bioavailability study in albino rabbits showed three times improvement in oral bioavailability.

FORMULATION AND EVALUATION OF BILAYER SUSTAINED RELEASE TABLET OF ZOLPIDEM TARTRATE

The purpose of the present study was to develop a bilayer tablet of zolpidem tartrate (ZT) using sodium starch glycolate (SSG) as superdisintegrant in the immediate release (IR) layer and hydrophilic polymers such as hydroxypropyl methylcellulose (HPMC K4M), metalose 90 SH 4000, carbapol 974 PNF in sustained release (SR) layer. Both the IR and SR granules of ZT were evaluated for bulk density, tapped density, angle of repose, Carr’s index, Hausner ratio and loss on drying. All the values were found to be satisfactoy. The prepared bilayer tablets were evaluated for weight variation, hardness, friability, drug content, in vitro drug release, FT-IR studies, similarity factor and stability studies. In vitro dissolution studies were carried out in a USP dissolution apparatus I using 500mL of 0.01N HCl as dissolution medium. The formulations gave an initial burst effect to provide the loading dose of the drug followed by sustained release for 4 h. The data obtained were fitted to Zero order, First order, Higuchi’s model and Korsmeyer-Peppas equations. The release exponent (n) values for all the formulations were less than 0.45 indicating Fickian diffusion was the drug release mechanism. FT-IR studies indicated that there are no drug-excipient interactions. The similarity factor (f2) was calculated by comparing dissolution data of all the formulations with that of marketed bilayer tablet of ZT (Ambien CR). The f2 value was highest (70) for the formulation SF8 and was selected as promising formulation among all the developed formulations. The stability study was performed on the formulation SF8 at 25oC/60% RH, 30oC/75% RH and 40oC/75% RH (accelerated condition) for 3 months. The results indicated that there were no significant changes in aforesaid tablet properties. Key words: bilayer tablets, zolpidem tartrate, sustained release, higuchi’s equation, similarity factor

Development and evaluation of orodispersible sustained release formulation of amisulpride–γ-cyclodextrin inclusion complex

Amisulpride (AMI) is an atypical antipsychotic having poor aqueous solubility and poor oral bioavailability. Inclusion complex between AMI and gamma cyclodextrin (γ-CD) was prepared by kneading method using 1:1 stoichiometry. Solubility of AMI was enhanced by 3.74 times after inclusion complex formation. Amisulpride–γ-cyclodextrin inclusion complex was characterized by FTIR, DSC and XRD techniques. Further sustained release granules of Amisulpride–γ-cyclodextrin inclusion complex (CDSR) were prepared by treating complex with molten stearic acid. Drug release from CDSR granules was sustained up to 12 h with 100 % stearic acid proportion. The integrity of AMI–γ-CD inclusion complex in lipid phase was assessed by XRD study. Finally orodispersible tablets of CDSR granules (OD-CDSR) were prepared using Ac-Di-Sol and microcrystalline cellulose. Disintegration time was assessed by both pharmacopoeial and modified method. Optimized formulation was rapidly disintegrated within 25 s. Thus solubility enhancement and sustained release of AMI was achieved by orodispersion of CDSR granules for improvement of patient compliance.