Effect of various disintegrants on the availability of directly compressed sulphadimidine tablets

Sulphadimidine tablets were prepared using 50% w/w of the following vehicles, Celutab, anhydrous lactose and Avicel. Various disintegrants 5% w/w were also incorporated e.g. Primojel, Veegum F, Amberlite, STA-Rx, Meprogat and Alginate YZ. It was found that the disintegration time of the various tablets containing different disintegrants was considerably decreased. The disintegrants increased also the dissolution rate of the various tablet formulations containing sulphadimidine by different extent. The variations in the dissolution rate among the various tablet formulations may be due to the difference in the nature of the disintegrants and their mechanism of action and possibly their interactions with the drug or the vehicle.     

Development of a buccal bioadhesive nicotine tablet formulation for smoking cessation

Bioadhesive buccal tablet formulations for delivery of nicotine into the oral cavity were developed. Carbomer (Carbopol)974P NF) (CP) and alginic acid sodium salt (NaAlg) were used as bioadhesive polymers in combination with hydroxypropyl methylcellulose (HPMC) at different ratios. Magnesium carbonate was incorporated into the formulations as a pH increasing agent. In vitro release and bioadhesion studies were performed on the developed tablets. In the formulations containing CP:HPMC, the NHT released increased with the increasing HPMC concentration whereas a decrease was observed with increasing HPMC concentration in formulations containing NaAlg:HPMC. The bioadhesive properties of the tablets containing NaAlg:HPMC was not affected by the concentration of the NaAlg (P>0.05) but increased significantly with the increasing CP concentration (P>0.05). A decrease in pH of the dissolution medium to acidic values was avoided by incorporation of magnesium hydroxide into the formulations. The developed formulations released NHT for 8h period, and remained intact except for the formulation containing CP:HPMC at 20:80 ratio.     

Release Kinetics of Papaverine Hydrochloride from Tablets with Different Excipients

The influence of excipients on the disintegration times of tablets and the release of papaverine hydrochloride (PAP) from tablets were studied. Ten different formulations of tablets with PAP were prepared by direct powder compression. Different binders, disintegrants, fillers, and lubricants were used as excipients. The release of PAP was carried out in the paddle apparatus using 0.1 N HCl as a dissolution medium. The results of the disintegration times of tablets showed that six formulations can be classified as fast dissolving tablets (FDT). FDT formulations contained Avicel PH 101, Avicel PH 102, mannitol, (3-lactose, PVP K 10, gelatinized starch (CPharmGel), Prosolv Easy Tab, Prosolv SMCC 90, magnesium stearate, and the addition of disintegrants such as AcDiSol and Kollidon CL. Drug release kinetics were estimated by the zero- and first-order, Higuchi release rate, and Korsmeyer-Peppas models. Two formulations of the tablets containing PVP (K10) (10%), CPharmGel (10% and 25%), and Prosolv Easy Tab (44% and 60%) without the addition of a disintegrant were well-fitted to the kinetics models such as the Higuchi and zero-order, which are suitable for controlled- or sustained-release.     

Effect of formulation solubility and hygroscopicity on disintegrant efficiency in tablets prepared by wet granulation, in terms of dissolution

The effect of tablet formulation solubility and hygroscopicity on the dissolution efficiency of three "super disintegrants" (sodium starch glycolate, crospovidone, and croscarmellose sodium) in tablets prepared by wet granulation was investigated. Lactose, calcium phosphate dibasic, sorbitol, and naproxen sodium, alone or in combination, provided varying degrees of solubility and hygroscopicity in the formulations. To monitor in vitro dissolution, 1% p-aminobenzoic acid was added to the formulation as a tracer. The results indicate that highly soluble and/or hygroscopic ingredients decrease the effectiveness of super disintegrants in promoting in vitro dissolution. The greater the overall hygroscopicity and solubility of the tablet formulation, the larger the decrease in the efficiency of the super disintegrant.     

Design and optimization of floating drug delivery system of acyclovir

The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 3(2) full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t(50%)) and 70% (t(70%)) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t(50%) and t(70%) indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix.     

Effect of the mode of incorporation on the disintegrant properties of acid modified water and white yam starches

Acid modified starches obtained from two species of yam tubers namely white yam – Dioscorea rotundata L. and water yam – D. alata L. DIAL2 have been investigated as intra- and extra-granular disintegrants in paracetamol tablet formulations. The native starches were modified by acid hydrolysis and employed as disintegrant at concentrations of 5 and 10% w/w and their disintegrant properties compared with those of corn starch BP. The tensile strength and drug release properties of the tablets, assessed using the disintegration and dissolution (t₅₀ and t₈₀ – time required for 50% and 80% of paracetamol to be released) times, were evaluated. The results showed that the tensile strength and the disintegration and dissolution times of the tablets decreased with increase in the concentration of the starch disintegrants. The acid modified yam starches showed better disintegrant efficiency than corn starch in the tablet formulations. Acid modification appeared to improve the disintegrant efficiency of the yam starches. Furthermore, tablets containing starches incorporated extragranularly showed faster disintegration but lower tensile strength than those containing starches incorporated intragranularly. This emphasizes the importance of the mode of incorporation of starch disintegrant.     

Formulation and evaluation of famotidine floating tablets

The purpose of this investigation was to prepare a gastroretentive drug delivery system of famotidine. Floating tablets of famotidine were prepared employing two different grades of methocel K100 and methocel K15M by effervescent technique; these grades of methocel were evaluated for their gel forming properties. Sodium bicarbonate was incorporated as a gas-generating agent. The floating tablets were evaluated for uniformity of weight, hardness, friability, drug content, in vitro buoyancy and dissolution studies. The effect of citric acid on drug release profile and floating properties was investigated. The prepared tablets exhibited satisfactory physico-chemical characteristics. All the prepared batches showed good in vitro buoyancy. The tablet swelled radially and axially during in vitro buoyancy studies. It was observed that the tablet remained buoyant for 6-10 hours. Decrease in the citric acid level increased the floating lag time but tablets floated for longer duration. A combination of sodium bicarbonate (130mg) and citric acid (10mg) was found to achieve optimum in vitro buoyancy. The tablets with methocel K100 were found to float for longer duration as compared with formulations containing methocel K15M. The drug release from the tablets was sufficiently sustained and non-Fickian transport of the drug from tablets was confirmed.     

Novel buccal adhesive system for anti-hypertensive agent Nimodipine

Novel buccal adhesive system (NBAS) containing Nimodipine (N) was prepared and evaluated by different parameters such as weight uniformity, thickness, hardness, surface pH, swelling index, mucoadhesive strength (MS), in vitro drug release and ex vivo drug permeation. Different formulations containing 5–20% Carbopol 934 (CP) and SCMC HV in sustained release part and sodium alginate:chitosan lactate in different ratios (1:1, 2:1, 1:2, and 3:1) in fast release part were prepared and tested. NBAS containing CP 5% and SCMC HV and sodium alginate: chitosan lactate 1:1 was selected as a suitable formula based on the (MS) and the release profile. Compared to the conventional buccal adhesive tablet, NBAS showed an effective controlled release pattern with faster release at the initial period. The mechanism of N release was found to be by non-fickian diffusion, followed first order release kinetics. It can be considered that NBAS is a superior, novel system that overcomes the drawback associated with the conventional buccal adhesive tablet.     

Oral controlled release formulation of diclofenac sodium by microencapsulation with ethyl cellulose

The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of diclofenac sodium (DFS) using different proportions of ethyl cellulose (EC) as the retardant material to extend the release. The formulated microcapsules were then compressed into tablets to obtain controlled release oral formulations. Phase separation-coacervation technique was employed to prepare microcapsules of DFS using different proportions of EC in cyclohexane. Physical characteristics of microcapsules and their tablets, in vitro release pattern of the designed microcapsules and their tablets prepared from them were studied using USP dissolution apparatus (USP 2000) type 2 (paddle method) in triple distilled water. The prepared microcapsules were white, free flowing and spherical in shape, with the particle size varying from 49.94-52.72 microm. The duration of DFS release from microcapsules was found to be directly proportional to the proportion of EC and, thus, coat thickness. All tablets were of good quality with respect to appearance, drug content uniformity, hardness, weight variation, friability and thickness uniformity. In vitro release study of the tabletted microcapsules in triple distilled water showed a zero order release kinetics and extended release beyond 24 h. A good correlation was obtained between drug release (t(60)) and proportion of EC in the microcapsules. In the case of tabletted microcapsules, very good correlation could be established between t(60), proportion of EC, weight of the tablets and between release rate constant (K) and proportion of EC. All the formulations were highly stable and possessed reproducible release kinetics across the batches.     

Water-sorption properties of tablet disintegrants.

The water-sorption properties of four tablet disintegrants, starch, sodium carboxymethylcellulose, sodium starch glycolate, and a cation-exchange resin, were examined in the form of powders and in compressed tablets prepared from calcium phosphate dibasic dihydrate. Dissolution properties of the tablets compare well to the water-sorption properties. The effect of storage in the presence of water vapor upon tablets containing the various disintegrants was evaluated in terms of tablet hardness and disintegration time. Differences in the effects produced in the various tablet formulations can be related to the differing mechanisms whereby the disintegrants effect tablet rupture. Photomicrographic data support the conclusions drawn from the water-sorption, disintegration, and dissolution studies. Sodium starch glycolate and the cation-exchange resin merit careful consideration by formulators using calcium phosphate dibasic dihydrate or similar direct compression matrixes.     

pH-independent drug release of an extremely poorly soluble weakly acidic drug from multiparticulate extended release formulations.

Extended release mini matrix tablets for 8-Prenylnaringenin (8-PN), an extremely poorly soluble weakly acidic drug, were developed by using polyvinylacetate/polyvinylpyrrolidone as matrix former. Mini matrix tablets were manufactured by direct compression or wet granulation technique. With conventional modified release formulations, the drug demonstrated pH-dependent release due to pH-dependent solubility of the drug substance (i.e., increasing solubility at higher pH-values). In order to achieve pH-independent drug release two classes of pH-modifying agents (water-soluble vs. water-insoluble) were studied with respect to their effect on the dissolution of 8-PN. Addition of water-soluble salts of weak acids (sodium carbonate and sodium citrate) failed in order to achieve pH-independent 8-PN release. In contrast, addition of water insoluble salts of a strong base (magnesium hydroxide and magnesium oxide) was found to maintain high pH-values within the mini matrix tablets during release of 8-PN at pH 1 over a period of 10 h. The micro-environmental conditions for the dissolution of the weakly acidic drug were kept almost constant, thus resulting in pH-independent drug release. Compound release from mini matrix tablets prepared by wet granulation was faster compared to the drug release from tablets prepared by direct compression.     

Oral controlled release formulation of diclofenac sodium by microencapsulation with ethyl cellulose

The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of diclofenac sodium (DFS) using different proportions of ethyl cellulose (EC) as the retardant material to extend the release. The formulated microcapsules were then compressed into tablets to obtain controlled release oral formulations. Phase separation-coacervation technique was employed to prepare microcapsules of DFS using different proportions of EC in cyclohexane. Physical characteristics of microcapsules and their tablets, in vitro release pattern of the designed microcapsules and their tablets prepared from them were studied using USP dissolution apparatus (USP 2000) type 2 (paddle method) in triple distilled water. The prepared microcapsules were white, free flowing and spherical in shape, with the particle size varying from 49.94-52.72 #119 m. The duration of DFS release from microcapsules was found to be directly proportional to the proportion of EC and, thus, coat thickness. All tablets were of good quality with respect to appearance, drug content uniformity, hardness, weight variation, friability and thickness uniformity. In vitro release study of the tabletted microcapsules in triple distilled water showed a zero order release kinetics and extended release beyond 24 h. A good correlation was obtained between drug release (t 60) and proportion of EC in the microcapsules. In the case of tabletted microcapsules, very good correlation could be established between t 60, proportion of EC, weight of the tablets and between release rate constant (K) and proportion of EC. All the formulations were highly stable and possessed reproducible release kinetics across the batches.     

New oral solid dosage form for furosemide oral administration

Furosemide (FURO) is a drug labeled in class IV of the Biopharmaceutics Classification System (BCS) as it is both poor soluble and poor permeable. The aim of this work was to improve FURO biopharmaceutical properties by its formulation in a new solid oral dosage form. It consists in the realization of the composite MgAl-HTlc-FURO, obtained by FURO intercalation into the inorganic matrix hydrotalcite (MgAl-HTlc), and its successive formulation in tablets intended to be swallowed whole and to disintegrate rapidly in the stomach. These formulations were prepared by direct compression of a simple powder mixture constituted by MgAl-HTlc-FURO, a super disintegrant (Explotab, PolyplasdoneXL, PolyplasdoneXL-10, PolyplasdoneINF 10 or L-HPCLH-21) and a filler. The prepared formulations were submitted to disintegration time tests, and only those displaying the lowest disintegration time in gastric medium were submitted to in vitro release studies. Drug dissolution profiles from MgAl-HTlc-FURO tablets were compared with those containing crystalline FURO alone or physically mixed to MgAl-HTlc instead of MgAl-HTlc-FURO. The results revealed that tablets containing MgAl-HTlc-FURO give the best dissolution profile and that L-HPCLH-21 is able to promote the highest drug release in gastric medium, resulting in the most suitable super disintegrant in comparison with the other tested.     

Eudraginated polymer blends: a potential oral controlled drug delivery system for theophylline

Sustained release (SR) dosage forms enable prolonged and continuous deposition of the drug in the gastrointestinal (GI) tract and improve the bioavailability of medications characterized by a narrow absorption window. In this study, a new strategy is proposed for the development of SR dosage forms for theophylline (TPH). Design of the delivery system was based on a sustained release formulation, with a modified coating technique and swelling features aimed to extend the release time of the drug. Different polymers, such as Carbopol 71G (CP), sodium carboxymethylcellulose (SCMC), ethylcellulose (EC) and their combinations were tried. Prepared matrix tablets were coated with a 5 % (m/m) dispersion of Eudragit (EUD) in order to get the desired sustained release profile over a period of 24 h. Various formulations were evaluated for micromeritic properties, drug concentration and in vitro drug release. It was found that the in vitro drug release rate decreased with increasing the amount of polymer. Coating with EUD resulted in a significant lag phase in the first two hours of dissolution in the acidic pH of simulated gastric fluid (SGF) due to decreased water uptake, and hence decreased driving force for drug release. Release became faster in the alkaline pH of simulated intestinal fluid (SIF) owing to increased solubility of both the coating and matrixing agents. The optimized formulation was subjected to in vivo studies in rabbits and the pharmacokinetic parameters of developed formulations were compared with the commercial (Asmanyl(?)) formulation. Asmanyl(?) tablets showed faster absorption (t(max) 4.0 h) compared to the TPH formulation showing a t(max) value of 8.0 h. The C(max) and AUC values of TPH formulation were significantly (p < 0.05) higher than those for Asmanyl(?), revealing relative bioavailability of about 136.93 %. Our study demonstrated the potential usefulness of eudraginated polymers for the oral delivery of the sparingly soluble drug theophylline.     

Formulation design and optimization of fast disintegrating Lorazepam tablets by effervescent method

Fast disintegrating tablets of lorazepam were prepared by effervescent method with a view to enhance patient compliance. A 3(2) full factorial design was applied to investigate the combined effect of two formulation variables: amount of crospovidone and mixture of sodium bicarbonate, citric acid and tartaric acid (effervescent material) on in vitro dispersion time. Crospovidone (2-8% w/w) was used as superdisintegrant and mixture of sodium bicarbonate, citric acid and tartaric acid (6-18% w/w) was used as effervescent material, along with directly compressible mannitol to enhance mouth feel. The tablets were evaluated for hardness, friability, thickness, drug content uniformity and in vitro dispersion time. Based on in vitro dispersion time (approximately 13 s); the formulation containing 8% w/w crospovidone and 18% w/w mixture of sodium bicarbonate, citric acid and tartaric acid was found to be promising and tested for in vitro drug release pattern (in pH 6.8 phosphate buffer), short-term stability and drug-excipient interaction. Surface response plots are presented to graphically represent the effect of independent variables (concentrations of crospovidone and effervescent material) on the in vitro dispersion time. The validity of the generated mathematical model was tested by preparing two extra-design check point formulations. The optimized tablet formulation was compared with conventional marketed tablet for drug release profiles. This formulation showed nearly eleven-fold faster drug release (t(50%) 2.8 min) compared to the conventional commercial tablet formulation (t(50%) >30 min). Short-term stability studies on the formulation indicated that there were no significant changes in drug content and in vitro dispersion time (P<0.05).     

挤出滚圆法制备尼群地平缓释微丸的处方因素考察

目的 对影响药物释放的处方因素进行考察.方法 以微晶纤维素（MCC）为成型辅料，乙基纤维素（EC）为缓释材料，可溶性高分子材料为致孔剂，乳糖、十二烷基硫酸钠（SDS）及崩解剂为释药速度调节剂，采用挤出滚圆法制备尼群地平固体分散体及微丸，通过体外释放度试验对各辅料的种类及用量进行详细考察。结果 在尼群地平含量为10％的前提下，EC（10cps）用量在20％左右有一定的缓释作用；致孔剂采用PVPkm用量应在5％以下；崩解剂种类及用量对微丸中药物的释放影响显著，4％～12％的交联羧甲基纤维素钠（CCNa）可使药物释放较为完全；乳糖及SDS对药物释放无明显影响，用量分别为20％和4％较佳；成球辅料MCC型号为AvicelPH101。结论 采用上述处方，可制得体外释放度符合要求的尼群地平缓释微丸。     

介质对硝苯地平缓释制剂溶出行为的影响

研究硝苯地平的两种国产普通片、一种进口缓释片和自制缓释微球在不同介质中的溶出行为。结果发现，介质对硝苯地平制剂的溶出速度有很大影响。以２０％乙醇水溶液或０．５％十二烷基硫酸钠水溶液为介质，缓释片和缓释微球的溶出太快，且不能区别各制剂的溶出度差异。在０．１ｍｏｌ／Ｌ盐酸或ｐＨ６．８磷酸盐缓冲液中加入０．０２％或０．１％吐温－８０，分别作为介质，能较好评价制剂的溶出行为。在含０．０２％吐温－８０的０．１ｍｏｌ／Ｌ盐酸溶液中投入微球２、５和１０ｍｇ对溶出度无显著影响。     

Optimization of drug release from compressed multi unit particle system (MUPS) using generalized regression neural network (GRNN)

The purpose of this study was development of diclofenac sodium extended release compressed matrix pellets and optimization using Generalized Regression Neural Network (GRNN). According to Central Composite Design (CCD), ten formulations of diclofenac sodium matrix tablets were prepared. Extended release of diclofenac sodium was acomplished using Carbopol® 71G as matrix substance. The process of direct pelletisation and subsequently compression of the pellets into MUPS tablets was applied in order to investigate a different approach in formulation of matrix systems and to achieve more control of the process factors over the principal response — the release of the drug. The investigated factors were X₁ -the percentage of polymer Carbopol® 71 G and X₂- crushing strength of the MUPS tablet. In vitro dissolution time profiles at 5 different sampling times were chosen as responses. Results of drug release studies indicate that drug release rates vary between different formulations, with a range of 1 hour to 8 hours of dissolution. The most important impact on the drug release has factor X₁ -the percentage of polymer Carbopol® 71 G. The purpose of the applied GRNN was to model the effects of these two causal factors on the in vitro release profile of the diclofenac sodium from compressed matrix pellets. The aim of the study was to optimize drug release in manner wich enables following in vitro release of diclofenac sodium during 8 hours in phosphate buffer: 1 h: 15–40%, 2 h: 25–60%, 4 h: 35–75%, 8 h: >70%.     

Sustained release of water-soluble drug from directly compressed alginate tablets

The release of acetyl salicylic acid from directly compressed alginate tablets was investigated. The effect of the amount and type of alginate on the drug release rate was evaluated in different formulations. Four different grades of alginate were used. The in vitro release studies were carried out using the apparatus II (paddle) equipment as described in the USP 23/NF dissolution monograph. Dissolution medium was 0.1 M HCl for 2 h followed by phosphate buffer pH 6.8; both at 37 degrees C. Sustained drug release up to 16 h was achieved using sodium alginate in combination with dibasic calcium phosphate.     

Diclofenac sodium multisource prolonged release tablets--a comparative study on the dissolution profiles

The aim of this work was to compare the dissolution behaviour of six diclofenac sodium prolonged release tablets of different brands obtained from the national market. The formulations contain the same amount of drug substance but different types and/or amount of excipients. The influence of these differences in formulation on the release characteristics of the dosage forms was evaluated on the European Pharmacopoeia apparatus 2 (paddle) employing eight different dissolution media in the pH range 1.2-8. Friability and hardness were tested too according to the European Pharmacopoeia. Dissolution profiles obtained from the studied formulations showed that the release characteristics vary considerably among different manufacturers and that even identical formulations show rather dissimilar release profiles in all the studied media. Use of both SIF without pancreatin and SIF without pancreatin containing 1% (w/v) Tween 20 resulted in strong discrimination among products. A correlation between friability and hardness and in vitro dissolution was evidenced for two formulations having identical excipient composition.