Hard Gelatin Capsules Research Articles

Cryogenic Fabrication of Dry Powders to Enhance the Solubility of a Promising Anticancer Drug, SHetA2, for Oral Administration.

SHetA2 is a novel anticancer drug with poor aqueous solubility. In formal toxicological studies, Kolliphor HS 15 was used as a solubilizing agent to increase the oral bioavailability of SHetA2. The purpose of this study was to formulate SHetA2 and Kolliphor HS 15 as solid powders to facilitate their filling in hard gelatin capsules for clinical trials. Two manufacturing processes, ultra-rapid freeze-drying (URFD) and spray freeze drying (SFD), were employed to fabricate solid powders of SHetA2-Kolliphor HS 15 and trehalose. The morphology, size, flowability, and compressibility of URFD-SHetA2 and SFD-SHetA2 powders were characterized. The crystallinity and apparent maximum solubility of SHetA2 in both powders were also determined. SFD-SHetA2 powders were spherical in shape, small, and with a wide size distribution while the URFD-SHetA2 powders were irregularly shaped and big but with a narrower distribution. DSC and XRD analyses indicated that SHetA2 was mostly amorphous in both powders. The flow of both powderswas categorized as "good" (angle of repose < 35°). The uniformity of drug content in URFD-SHetA2 powders was more variable than that in SFD-SHetA2 powders. The solubility profile of SHetA2 in both powders SGF exhibited a transient supersaturation "spring effect" due to the drug's amorphousness followed by extended supersaturation "parachute effect" at approximately 6μg/ml for both powders compared to 0.02 ± 0.01μg/ml for unprocessed drug. In conclusion, both URFD and SFD formed solid SHetA2 Kolliphor powders that are possible formulation candidates to be filled in hard gelatin capsules for clinical trials.

Potential Toxic Effects of Olanzapine on Metabolic Parameters in &amp;lt;i&amp;gt;de Novo&amp;lt;/i&amp;gt; Paranoid Schizophrenic Patients. The Role of Adjunctive Aripeprazole: Clinical and Experimental Study

Background: Approximately 75% of all deaths in people with schizophrenia are caused by physical illness with cardiovascular disease [CVD] being the commonest cause of death. Factors predisposing people with schizophrenia to CVD include antipsychotic medication. Aim of Work: The aim of this study was to detect metabolic syndrome and its components in de novo paranoid schizophrenics on olanzapine therapy and the metabolic benefits of addition of aripeprazole, clinically and experimentally. Methodology: 1) Clinical study: 200 Outpatients suffered from de novo paranoid schizophrenia according to 10th International Classification of Psychiatric Disorders, Research Criteria [ICD10 RC] were included in the study. None of them had any component of metabolic syndrome. They were maintained on olanzapine [10 - 20 mg]. Patients were assessed clinically, psychometrically using Scale for the Assessment of Negative [SANS] and Positive [SAPS] Symptoms and metabolically at base line and after 6 months. Patients who had metabolic syndrome after 6 month of starting olanzapine therapy, were randomly divided into two groups according to added regime to maintained olanzapine: Group 1: olanzapine [10 mg/day] + placebo [empty hard gelatin capsule]. Group II: olanzapine [10 mg/day] + aripeprazole [10 mg/day]. 2) Experimental study: 40 male albino rats were randomly equally divided into 4 groups: Group 1 [control group]: received a standard diet, Group II [olanzapine treated]: received olanzapine at a dose of 0.5 mg/kg/day, Group III [aripiprazole treatd]: received aripiprazole at a dose of 2 mg/kg/day, Group IV [combined olanzapine and aripiprazole treated]: received olanzapine at a dose of 0.5 mg/kg/day combined with aripiprazole at a dose of 2 mg/kg/day orally. The duration of the study was 16 weeks. All treated rat groups were assessed for metabolic parameters, liver enzymes and histopathology. Results: Clinically, after the 6 months of olanzapine treatment [mean dose 12.75 mg], there was significant increase [p < 0.001] in weight, body mass index, triglyceride, total cholesterol, and fasting blood glucose level compared to base line level of these parameters (Table 1). 32 patients [16%] suffered from metabolic syndrome after 6 months of olanzapine therapy. After 3 months of aripeprazole, [10 mg/day], addition to maintained olanzapine therapy to patients suffered from metabolic syndrome, there was significant [p < 0.001] improvement in tested parameters (Table 2). Experimentally, the rats in group II [olanzapine treated rats] had significantly higher body weight [p = 0.002], liver weight [p < 0.001], metabolic parameters [p < 0.001] and liver enzymes [p < 0.001] than controls. Group 1v [combined olanzapine and aripeprazole treated rats] had significant decrease in metabolic parameters and liver enzymes in comparison to olanzapine treated rats (Table 3). Histopathologically, liver fat cells were significantly [p < 0.001] present in the olanzapine-only [8 rats] treatment group compared to group 1v [3 rats] and group 11 [zero]. Liver fat cells were higher in number and larger in size in group 1 compared to group 1v and group 1. Conclusion and Recommendation: Olanzapine treatment was found to be associated with risk factors of metabolic syndrome clinically and experimentally and its hepatic manifestation of non-alcoholic fatty liver disease in wister rats. Improvements were observed clinically and experimentally in metabolic measures, liver enzymes and liver histopathology by addition of aripeprazole. Patients on olanzapine therapy must be followed regularly regarding metabolic parameters, hepatic, cardiac and cerebrovascular morbidity, with urgent interference with early manifestations. It is recommended to check liver enzymes regularly for those patients kept on atypical antipsychotic drug [olanzapine].

Příprava tvrdých želatinových tobolek s klesajícím obsahem diazepamu k léčbě závislosti na benzodiazepinech a Z -hypnoticích

V soucasne době existuji v celem v světě miliony lidi zavislých na benzodiazepinech. Forma somaticke i psychicke zavislosti znemožňuje okamžite vysazeni leciv. Jednim z dlouhodobě osvědcených lecebných postupů je převedeni pacientů na diazepam, který ma dlouhý biologický polocas. Po stabilizaci nasleduje postupne snižovani davek až do stavu placeba. Vhodnou lekovou formou se jevi tvrde želatinove tobolky, ve kterých mohou být kromě diazepamu obsaženy i dalsi adjuvantni leciva z řady antipsychotik, antidepresiv a betablokatorů, zmirňujicich abstinencni přiznaky. Vzhledem k nizkým davkam leciv musi mit tobolky vyhovujici obsahovou stejnoměrnost dle požadavků CL 2017. V běžne lekarenske praxi se nepodařilo tomuto požadavku vyhovět. Při použiti vhodneho plniva a běžneho kuchyňskeho mixeru je ale možne požadavek splnit. Výsledkem jsou tobolky s obsahem diazepamu v rozsahu 2,125 až 0,492 mg, urcene ke snižovani davky o 15 %. Zvolena technologie zaruci způsobilost procesu, a je tedy schopna produkovat/vyrabět tobolky v ramci tolerovaneho rozmezi hodnot pro hmotnostni a obsahovou stejnoměrnost.

Formulation Studies of Solid Self-Emulsifying Drug Delivery System of Ivermectin.

The suggested dose of ivermectin is 300 μG/kg/day for onchocerciasis but it has low water solubility and poor oral bioavailability. To prepare and evaluate a solid lipid-based self-emulsifying drug delivery system of ivermectin. Based on supersaturated solubility study, oil, surfactant, and co-surfactant were selected. On the basis of ternary phase diagrams and simplex-lattice design, self-emulsifying, drug delivery formulations had been developed and optimized. Ivermectin-excipients compatibility studies were performed using differential scanning calorimetry and Fourier transform infrared spectroscopy. Solid self-emulsifying drug delivery formulation was formulated from the optimized batch by surface assimilation method and filled into hard gelatin capsules. In vitro release rate and in vivo pharmacokinetic parameters of ivermectin from the capsules were determined. Two-tailed paired t-test/Dunnett multiple comparison tests were performed for in vivo pharmacokinetic parameter at 95 % of confidence level. Soybeans oil, tween 80, and span 80 were selected as oil, surfactant, and co-surfactant respectively. The ternary diagrams were shown the maximum area for emulsion in 1:2 surfactant/co-surfactant ratio. The optimized batch had found with 30 mg ivermectin, 6.17 g soybeans oil, 0.30 g tween 80, and 3.50 g span 80. All differential scanning calorimetry and Fourier transform infrared characteristic peaks of the optimized formulation were identical with that of pure ivermectin. The area under the curve of ivermectin from the capsule was about two-fold higher than that of ivermectin suspension. Solid self-emulsifying drug delivery system was an effective oral solid dosage form to improve the oral bioavailability of ivermectin.

Fabrication and Characterization of Electrospun Nanofibers for the Modified Release of the Chronobiotic Hormone Melatonin.

Objective: Aiming at the modified release of melatonin (MLT), electrospun-MLT loaded nano-fibers, filled into hard gelatin and DRcapsTM capsules, were used as formulants.Methods: Cellulose acetate, polyvinylpyrrolidinone and hydroxypropylmethylcellusose (HPMC 2910) were used for the preparation of the fiber matrices through electrospinning. The in vitro modified release profile of MLT from the fabricated matrices in gastrointestinal-like fluids was studied. At pH 1.2, the formulations CA1, CA2, PV1, HP1, HP2 and the composite formulations CAPV1-CAPV5 in hard gela-tin capsules exhibited fast MLT release.Results: In general, the same trend was observed at pH 6.8, with the exception of CAPV1 and CAPV2. These two composite formulations delivered 52.08% and 75.25% MLT, respectively at a slower pace (6 h) when encapsulated in DRcapsTM capsules. In all other cases, the release of MLT from DRcapsTM cap-sules filled with the MLT-loaded nanofibers reached 100% at 6h.Conclusion: These findings suggest that the MLT-loaded nanofibrous mats developed in this study ex-hibit a promising profile for treating sleep dysfunctions.

Pharmacokinetics and pharmacodynamics of glimepiride polymorphs

Glimepiride (GLIM) is used as an oral antihyperglycemic agent for treatment of type 2 diabetes. The drug presents two polymorphic forms (GLIM form I and GLIM form II) described in the literature, and according to in vitro data, GLIM form II is about 3.5 times more soluble and releases 2 times the drug amount than GLIM form I in the physiological pH range. Considering the literature in vitro data and that the diabetes treatment demands glycemic control, avoiding abrupt fluctuations in the blood glucose levels, this work aimed to study the impact of GLIM polymorphism in the in vivo performance of GLIM solid oral dosages. For this, hard gelatin capsules with GLIM form I or II were prepared and orally administered in rats. After that, pharmacokinetic studies were performed by sampling animal blood at different times, and biochemical parameters (pharmacodynamic), such as glucose and insulin, were also evaluated. Our results showed that the in vitro data corroborate with our in vivo assays. GLIM form II provided higher plasma concentration of drug than form I (at baseline up to approximately 200 min after oral administration) and, consequently, increased insulin release and reduced levels of glucose, showing good correlation between pharmacokinetic and pharmacodynamics assays. Thus, this study demonstrated that GLIM polymorphs in oral dosages might alter the drug efficacy, which may expose the patients to risks, such as hypoglycemia.

Impact of capsule type on aerodynamic performance of inhalation products: A case study using a formoterol-lactose binary or ternary blend

The aerodynamic performance of a dry powder for inhalation depends on the formulation and the dry powder inhaler (DPI). In the case of capsule-based DPIs, the capsule also plays a role in the powder aerosolisation and the dispersion of the micronized drug during the inhalation. This study evaluated the impact of gelatine capsules (Quali-G™ and Hard Gelatine Capsules for DPIs), cold-gelled hypromellose (HPMC) capsules (Quali-V®-I and Vcaps®) and thermal-gelled HPMC capsules (Vcaps®Plus) from Qualicaps® and Capsugel® respectively, on the delivered dose (DD), fine particle dose (FPD), and capsule retention for formoterol-lactose binary and ternary blends. This study used a low resistance Axahaler® DPI based on the RS01 design (Plastiape, Italy). Similar trends were observed with the different capsule types that packaged both dry powder formulations. The highest DD and FPD and the lowest formoterol capsule retention were observed with cold-gelled HPMC capsules such as Quali-V-I® and Vcaps®, without significant differences between these capsules (p > 0.05, one-way ANOVA with Newman-Keuls post-hoc test) for both dry powders. Therefore, the capsule composition and manufacturing process have an influence on aerodynamic performance. In addition, the ternary blend showed higher DDs and FPDs but also higher capsule retention in comparison to the binary blend.

Oral Modified Release Multiple-Unit Particulate Systems: Compressed Pellets, Microparticles and Nanoparticles.

Oral modified-release multiparticulate dosage forms, which are also referred to as oral multiple-unit particulate systems, are becoming increasingly popular for oral drug delivery applications. The compaction of polymer-coated multiparticulates into tablets to produce a sustained-release dosage form is preferred over hard gelatin capsules. Moreover, multiparticulate tablets are a promising solution to chronic conditions, patients’ adherence, and swallowing difficulties if incorporated into orodispersible matrices. Nonetheless, the compaction of multiparticulates often damages the functional polymer coat, which results in a rapid release of the drug substance and the subsequent loss of sustained-release properties. This review brings to the forefront key formulation variables that are likely to influence the compaction of coated multiparticulates into sustained-release tablets. It focusses on the tabletting of coated drug-loaded pellets, microparticles, and nanoparticles with a designated section on each. Furthermore, it explores the various approaches that are used to evaluate the compaction behaviour of particulate systems.

Self-nanoemulsifying drug-delivery systems for potentiated anti-inflammatory activity of diacerein.

BackgroundEffective treatment of osteoarthritis necessitates both symptomatic relief and hindrance of joint degeneration progression. Non-steroidal anti-inflammatory drugs permit symptomatic relief only and can cause mucosal injury in the gut. Before absorption, diacerein (Dcn) is converted into rhein that counteracts cartilage degeneration without affecting prostaglandin production. Yet, low solubility and laxative action of unabsorbed rhein in the colon hindered its use. Thus, enhanced Dcn dissolution would allow absorption at the upper gut improving its bioavailability and possibly abolishing the laxative action.MethodsTherefore, self-nanoemulsifying drug delivery systems (SNEDDSs) with each of gelucire 44/14 (Glc) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) at different drug:carrier weight ratios of 1:1, 1:2, 1:4, 1:6, 1:8 and 1:10 were prepared by melt method and filled into hard gelatin capsules. The optimized binary systems were selected based on solid state characterization, scanning electron microscopy (SEM) and in vitro evaluation of the prepared SNEDDSs in comparison with their corresponding physical mixtures (PMs) and Dcn. The optimized systems were further examined with respect to their morphology, size distribution and ζ-potential. Moreover, the anti-inflammatory activity of the optimized systems against carrageenan-induced paw edema in rats was assessed through estimation of edema and edema inhibition percentages as well as histopathological examination and immunohistochemical localization of tumor necrosis factor-alpha (TNF-α) and caspase-3.ResultsSignificantly (P<0.05) enhanced in vitro drug release was recorded for SNEDDSs with either carrier when compared to Dcn and the corresponding PMs. SNEDDSs based on 1:10 Dcn:Glc and 1:8 Dcn:TPGS showed significantly (P<0.05) reduced edema and inflammation as well as expression of TNF-α and caspase-3 relative to positive control and Dcn pretreated groups.ConclusionThese SNEDDSs can be represented as potential oral drug delivery systems of Dcn for enhanced dissolution and anti-inflammatory activity against carrageenan-induced paw edema.

Clove Bud Polyphenols Alleviate Alterations in Inflammation and Oxidative Stress Markers Associated with Binge Drinking: A Randomized Double-Blinded Placebo-Controlled Crossover Study.

Acetaldehyde, the major cytotoxin formed by the metabolism of alcohol, is responsible for liver injury, extracellular matrix alterations, inflammation, and hangover in heavy drinkers. This study aimed to demonstrate the efficacy of a standardized polyphenolic extract of clove buds (Clovinol) in ameliorating the oxidative stress and inflammation caused by the accumulation of acetaldehyde after binge drinking. We used a randomized, double-blinded crossover study with 16 male social drinkers. The subjects were randomized into two groups of eight subjects and received either placebo or Clovinol in a single hard shell gelatin capsule (250 mg × 1) per day. The dosage of alcohol was 1 g/kg body weight/day. After 2 weeks of washout period, the treatment regime was reversed. Blood samples were drawn at 0, 0.5, 2, 4, and 12 h after treatment with either placebo or Clovinol, and biochemical parameters were analyzed. Hangover severity score was determined by using a validated questionnaire as reported earlier. Results showed faster elimination of blood acetaldehyde with significant decreases in oxidative stress, lipid peroxidation, C-reactive protein, interleukin-6, and significant enhancement in glutathione and superoxide dismutase as compared with placebo along with an overall reduction of 55.34% in hangover severity in Clovinol-treated subjects. This study demonstrated the efficacy of clove bud polyphenols for alleviating alcohol-related side effects among social drinkers at the studied dose.

Formulation and evaluation of curcumin microsponges for oral and topical drug delivery

The aim of the present study was to improve the release rate of curcumin by microsponges prepared through quasi-emulsion solvent diffusion technique using ethylcellulose and PVA as carriers. The microsponges were characterized by FTIR, DSC, XRD and SEM studies followed by determination of total drug content and entrapment efficiency. The prepared microsponges were further filled in hard gelatin capsule shell and then loaded in carbopol gel to evaluate its potential in oral and topical drug delivery. Further, it was observed from the studies on release rate that microsponges filled in hard gelatin capsule shells (batch MS4) showed 93.2% release of curcumin whereas pure curcumin filled in capsule showed only 11.7% release in 8 h study. Furthermore, the microsponges loaded in carbopol gel were evaluated for ex vivo drug deposition studies and it was found that 77.5% of the curcumin was released within 24 h. The estimated drug remained in the skin was 207.61 ± 5.03 μg/cm2 as determined by a Franz diffusion cell. The drug release profile data were found to be fitted best into the zero-order model with anomalous transport mechanism of drug release in both cases.

Porous Oral Drug Delivery System: Tablets

One of the most active and promising areas of research in this pharmaceutical field is the application of porous structures in solid-state pharmaceuticals, particularly given the large number of existing and emerging therapeutic molecules that are classified as poorly soluble, including approximately 40% of the top 200 oral drugs globally. Porous compacts have been extensively studied for pharmaceutical applications due to their good biocompatibility, biodegradability, and satisfactory solubility at low toxicity. Porous compacts can be filled in hard gelatine capsule shells or processed to form tablets. Porous formulations in the tablet form showed good biocompatibility without causing undesirable side effects in biological systems. The porous particulate drug formulations can be of both types such as immediate or sustained release delivery system. The evolution of porous matrices as potential drug delivery systems continues with ongoing efforts in improving the loading and controlled release of therapeutics, with particular interest in targeted delivery. The mechanism of immediate release from porous tablets can be attributed to quick entry of water into porous matrix which causes rapid disintegration and dissolution of the tablet. The oral bioavailability of poorly water-soluble drugs is enhanced by porous compacts. Porous compacts are also used to enhance the dissolution of relatively insoluble drugs.

Quality by design based development and optimization of novel gastroretentive floating osmotic capsules of clopidogrel bisulfate

The aim of the present investigation was to develop and optimize gastroretentive floating osmotic formulation of clopidogrel bisulfate using risk based approach. Risk assessment was carried out using failure mode effect analysis (FMEA) and high risk factors were identified. Preliminary studies highlighted importance of selection of low molecular weight PEO (molecular weight ~ 100,000) as rate controlling polymer and band sealing of coated capsules whereas thermal characterization studies assisted in selection of hydrogenated castor oil as more compatible lubricant. A face centered central composite design (CCD) was deployed to optimize high risk factors i.e. amount of osmogen (sodium chloride), amount of rate controlling polymer (Polyethylene oxide), polymer (Cellulose acetate) to plasticizer (PEG 3350) ratio in semipermeable membrane and weight gain per unit surface area. Optimized formulation was selected using constraint based graphical optimization technique and desirability function. Optimized batch was also found to be stable under selected packaging configurations. Optimized batch exhibited dissolution at 1 h of 4.65%, 4 h of 31.23%, 8 h of 62.80%, 12 h of 94.55% with zero floating lag time and total buoyancy time of more than 12 h. Scanning electron microscopy (SEM) was carried out to characterize semipermeable coating membrane before and after dissolution studies. Capability indices of six reproducible batches illustrated capability of selected process for manufacturing batches as per desired specifications. Overall, present investigation successfully illustrated development and optimization of novel hard gelatin capsule based gastroretentive floating osmotic formulation of clopidogrel bisulfate with zero order drug release profile and improved patient compliance.

Enhancing the Dissolution Stability of Hard Gelatin Capsules Using Activated Carbon as a Packaging Component

Hard gelatin capsule (HGC) shells are widely used to encapsulate drugs for oral delivery but are vulnerable to gelatin cross-linking, which can lead to slower and more variable in vitro dissolution rates. Adding proteolytic enzymes to the dissolution medium can attenuate these problems, but this complicates dissolution testing and is only permitted by some regulatory authorities. Here, we expand the scope of our previous work to demonstrate that canisters containing activated carbon (AC) or polymeric films embedded with AC particles can be used as packaging components to attenuate gelatin cross-linking and improve the dissolution stability of hard gelatin-encapsulated products under accelerated International Council for Harmonisation conditions. We packaged acetaminophen and diphenhydramine HCl HGCs with or without AC canisters in induction-sealed high-density polyethylene bottles and with or without AC films in stoppered glass vials and stored these samples at 50°C/75% relative humidity through 3 months and at 40°C/75% relative humidity for 6 months. Samples packaged with AC canisters or AC films dissolved more rapidly than samples packaged without AC when differences were observed. These results demonstrate that different sources and formats of AC can enhance the dissolution stability of HGCs packaged in bottles and other potential packaging systems such as blister cards.

Development and Characterisation of Modified Release Hard Gelatin Capsules, Based on In Situ Lipid Matrix Formation.

A new technology was developed to form extended release hard gelatin capsules, based on the lipid matrix formation of Gelucire 50/13 and cetostearyl alcohol. Matrices were formed in situ by filling pulverised lipids, ethylcellulose and active ingredients such as diclofenac sodium, acetaminophen and metronidazol into capsules and heating at 63°C for 11min. Effects of heating were investigated also on the brittleness of capsule shells. Inhibition of the evaporation of water reduced capsule damage. Dissolution tests and texture analysis were performed to discover the release and mechanical profiles of the matrices. Tests were repeated after 1month storage and results were compared. Gelucire 50/13 alone prolonged drug release but cetostearyl alcohol slowed drug liberation even further. Drug release from all compositions was found to follow first-order kinetic. Significant softening of the matrices was detected during storage in composition containing only Gelucire 50/13, ethylcellulose and diclofenac sodium. Thermal analysis and IR tests were also performed to discover physicochemical interactions between active pharmaceutical ingredients and excipients. Thermal analysis confirmed a notable interaction between diclofenac sodium and Gelucire 50/13 which could be the cause of the observed softening. In conclusion, modified release hard gelatin capsules were developed by a simple and fast monolithic lipid matrix formation method.

Extraction, formulation and evaluation of fast dissolving oral films of nicotine for smoking cessation

To produce oral films of nicotine in a laboratory setting to aid smokers in smoking cessation. Nicotine is a highly addictive drug and many people suffer from its addiction around the globe in the form of smoking. This problem is particularly pronounced in Pakistan and many smokers here do not have access to cessation medications. To prevent smokers from inhaling harmful chemicals like tar, carbon mono oxide and carcinogenic compounds produced from burning vegetable matter, pharmaceutical nicotine is used in the form of chewing gums, TDDS patches and oral films. The oral route is one of the most popular routes of drug administration because of its low cost, easy administration and a high rate of patient compliance. Many patients especially geriatric and paediatric ones have dysphagia or have some level of unease when swallowing hard gelatine capsules or solid tablets. This has led to the development of fast dissolving oral films. Fast dissolving oral thin-films are useful in patients such as paediatric, bedridden or developmentally disabled, geriatric patients, many of whom face difficulty in swallowing tablets or hard gelatine capsules. Oral fast dissolving films are a novel dosage form in which a thin film is prepared using hydrophilic polymers, which rapidly disintegrates or dissolves on the tongue or in the buccal cavity. Oral films are an alternative platform for molecules that undergo high first pass metabolism. Method: The method used here to prepare fast dissolving oral films is the solvent casting method. This method is fast, reliable, and extremely feasible in a laboratory setting. This simple method involves dissolving the ingredients to make a homogeneous solution and casting the said solution in a suitable container in order to produce oral films. Results: Using this method structurally sound films were obtained. These films were then tested; employing various parameters for this task. The results obtained hence thereof were sufficiently satisfying. Conclusion: The solvent casting method is a pragmatic and suitable approach to producing standard quality films in a laboratory. The concentrations of the polymer and the plasticizer may need to be adjusted according to the active pharmaceutical ingredient.

THE INFLUENCE OF HPC-L AND EUDRAGIT L30 D-55 ON DELAYED RELEASE OMEPRAZOLE MAGNESIUM MULTIPLE-UNIT PELLET SYSTEM

Objective: The objective of the study is to develop optimum, stable, delayed release pellets of omeprazole magnesium (20.6 mg dose). Omeprazole magnesium is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+ -ATPase at the secretory surface of the gastric parietal cell, which is orally administered drug, whereas omeprazole magnesium is degraded in stomach pH, so it is formulated as delayed release dosage form to absorb in intestinal pH.Methods: The formulation of delayed release pellets of omeprazole magnesium was developed by enteric film coating process varying the compositions of drug loading, barrier coating, and enteric coating using fluid bed processor. The prepared multiple pellets were filled into hard gelatin capsules as a single unit dosage forms.Results: The dissolution profile of formulation (F8) contains the efficient amount of hydroxypropyl cellulose-L and Eudragit L30 D55 leads to effective release of drug in 30 min. Fourier transform infrared and differential scanning colorimeter studies were conducted for the optimized formula to prove that the formula was not having incompatibility between the drug and excipients. The scanning electron microscopy studies were conducted to know the surface morphology of the pellets.Conclusion: It was concluded that optimized formulation (F8) shown good similarity with innovator. The results of the accelerated stability of final formulation revealed that storage conditions were excellent.

IN VITRO AND IN VIVO EVALUATION OF FLOATING GASTRORETENTIVE DRUG DELIVERY SYSTEM OF CIMETIDINE USING HARD ALGINATE CAPSULES

Objective: The objective of this study was to evaluate in vitro and in vivo of gastroretentive drug delivery system of cimetidine using hard alginate capsules.Methods: Drug release study was tested to various hard alginate capsules containing 200 mg cimetidine with paddle method dissolution apparatus in artificial gastric fluid pH 1.2. Concentrations of cimetidine were measured using ultraviolet spectrophotometer at 218.4 nm wavelength. The product that fulfilled the sustained release profile was evaluated for bioavailability using male rabbits at dose 9.3 mg/kg orally, and the antiulcer studies were evaluated by HCl-induced ulcer method at cimetidine dose 18 mg/kg once a day orally. Gastric lesions were evaluated by macroscopic and microscopic observations.Results: The results of drug release test showed that hard alginate capsule made from sodium alginate 500–600 cP gave sustained release profile of cimetidine for 12 h. In vivo bioavailability studies showed that cimetidine given with hard alginate capsules gave higher of Cmax, Tmax, and area under the curve of cimetidine compared to cimetidine that given with conventional hard gelatin capsules. The antiulcer studies showed that the healing effect of cimetidine that given with hard alginate capsules was faster than cimetidine given in suspension form. Cimetidine that given with hard alginate capsules macroscopically showed no gastric lesion and histopathologically also showed normal gastric mucosa of rats after 4 days treatment. However, cimetidine given in suspension form showed of 0.036±0.024 ulcer index and microscopically there was still erosion of gastric mucosa of rats after 4 days treatment.Conclusion: Floating gastroretentive of cimetidine using hard alginate capsules give a sustained release of cimetidine with better bioavailability and antiulcer effect of cimetidine.

DESIGN AND DEVELOPMENT OF MONTELUKAST SODIUM FAST DISSOLVING FILMS FOR BETTER THERAPEUTIC EFFICACY

The oral route is most popular route for the administration of therapeutic agents because of the low cost of therapy and ease of administration lead to high levels of patient compliance. The most popular oral solid dosage forms are tablets and capsules. Many patients find it difficult to swallow tablets and hard gelatin capsules particularly pediatric and geriatric patients and do not take their medicines as prescribed. The objective of this research was to prepare fast dissolving oral thin film (FDOTF) containing Montelukast sodium is indicated for the prophylaxis and chronic treatment of asthma to enhance convenience and compliance to the elderly and pediatric patients for better therapeutic efficacy. The present investigation was undertaken with the objective of formulating of the montelukast sodium fast dissolving oral thin films allowing fast reproducible drug dissolution in oral cavity thus bypassing first pass metabolism. The film were prepared by using polymers such as hydroxypropyl methyl cellulose (HPMC) and Maltodextrin, plasticizer such as PEG 400, by a solvent casting method. They were evaluated for physical characteristics such as thickness, uniformity of weight, folding endurance, drug content, surface ph, percentage elongation and tensile strength, drug polymers compatibility by FTIR study, scanning electron microscopy and in vitro drug release. The formulations were subjected to disintegration, in-vitro drug release test. The in vitro disintegration time of the optimized batch F4 was found to be 20 sec. The optimized batch was found to be stable for 1 month under specified stability conditions.

Comparative Characteristics of Anti-depressant, Anti-hypoxic Action, and Effect on the Physical Endurance of Scutellaria baicalensis Drugs.

The influence of original drugs from Scutellaria baicalensis (SB) Georgi (dry extract, powder of rhizomes and roots, tablets "Scutex" on the basis of the dry extract and capsules "Scutella", which contain powder of rhizomes with roots) was studied on depressive behavior, physical endurance and anti-hypoxic activity in mice. The used dry extract SB (SBDE), powder of roots and rhizomes from SB (SBRP), tablets from dry extract of SB named "Scutex", and hard gelatin capsules from the crushed root of SB named "Scutella" were obtained from National University of Pharmacy, Department of Industrial Technology of Drugs. In the experiment, 94 random-breed white male mice weighing 20-29 g were used and kept in standard sanitary and laboratory conditions. The experiments revealed that SBDE had anti-depressant action. Powder from rhizomes and roots of SB and "Scutella" capsules had anti-hypoxic action. All test drugs showed no influence on the physical endurance of mice. These results suggest the possible use of SBDE as an anti-depressant drug, and rhizomes with roots and "Scutella" capsules as an anti-hypoxic remedy. SBDE at a dose 50 mg/kg shows anti-depressant activity that exceeds the activity of the comparison drug "Bilobil". SBDE, SBRP, "Scutex" tablets and "Scutella" capsules do not affect the physical endurance of mice. SBDE at a dose 50 mg/kg and SBRP at a dose of 173 mg/kg and 260 mg/kg exhibit anti-hypoxic activity. "Scutex" tablets show no anti-hypoxic action and "Scutella" capsules cause probable anti-hypoxic action that exceeds the effect of the reference drug "Bilobil".