Mucoadhesive delivery systems. I. Evaluation of mucoadhesive polymers for buccal tablet formulation

Different types of mucoadhesive polymers, intended for buccal tablet formulation, were investigated for their comparative mucoadhesive force, swelling behavior, residence time and surface pH. The selected polymers were carbopols (CP934, and CP940), polycarbophil (PC), sodium carboxymethyl cellulose (SCMC) and pectin representing the anionic type, while chitosan (Ch) as cationic polymer and hydroxypropylmethyl cellulose (HPMC) as a non-ionic polymer. Results revealed that polyacrylic acid derivatives (PAA) showed the highest bioadhesion force, prolonged residence time and high surface acidity. SCMC and chitosan ensured promising bioadhesive characteristics, whilst HPMC and pectin exhibited weaker bioadhesion. Different polymer combinations as well as formulations were evaluated to improve the mucoadhesive performance of the tablets. Bioadhesive tablet formulations containing either 5% CP934, 65% HPMC and 30% spray-dried lactose or 2% PC, 68% HPMC and 30% mannitol showed optimum mucoadhesion and suitable residence time. SCMC, when formulated individually, exhibited promising bioadhesion, acceptable swelling, convenient residence time and surface pH. In-vivo trials of these formulations proved non-irritative and prolonged residence of the mucoadhesive tablets on human buccal mucosa for 8 to 13 h.     

Fast relief from migraine attacks using fast-disintegrating sublingual zolmitriptan tablets

Zolmitriptan is a potent molecule for treatment of migraine. Its current oral therapies present drawbacks such as slow onset of action, low bioavailability and large inter-subject variability. Fast disintegrating sublingual zolmitriptan tablet (FDST) using freeze-drying technique has been developed to enhance tablet disintegration and dissolution with the intention of speeding drug absorption and onset of effect, hence mitigating the effects on the gastrointestinal dysmotility that typically accompanies the migraine attack. The FDSTs were prepared using different concentrations of gelatin as binder and mannitol or L-alanine as matrix supporting/disintegration enhancing agents. The effect of formulation variables on the physicochemical and solid-state properties, as well as the dissolution behaviour of the tablets, was studied. The formulated FDSTs disintegrated within 30 s and showed significantly faster dissolution rate of zolmitriptan compared to the zolmitriptan oral tablet. Tablet containing 2% gelatin and mannitol showed acceptable weight variation, drug content and friability values. Furthermore, it had a low in-vitro and in-vivo disintegration time (11 s) and it reached 100% of drug release within 30 s. This sublingual formulation gave faster and higher zolmitriptan plasma concentration in rabbits compared to the oral zolmetriptan market product. Zolmitriptan FDST may therefore constitute an advance in the management of acute migraine attacks.     

Design and evaluation in vitro of controlled release mucoadhesive tablets containing chlorhexidine

This investigation deals with the development of buccal tablets containing chlorhexidine (CHX), a bis-bis-guanide with antimicrobial and antiseptic effects in the oral cavity, and able to adhere to the buccal mucosa to give local controlled release of drug. A mucoadhesive formulation was designed to swell and form a gel adhering to the mucosa and controlling the drug release into the oral cavity.

Some batches of tablets were developed by direct compression, containing different amounts of hydroxypropylmethylcellulose (HPMC) and carbomer; changing the amount ratio of these excipients in formulations, it is possible easily modulate the mucoadhesive effect and release of drug. The in vitro tests were performed using the USP 26/NF paddle apparatus, a specifically developed apparatus, and a modified Franz diffusion cells apparatus. This last method allows a simultaneous study of drug release rate from the tablets and drug permeation through the buccal mucosa.

Similar tests have also been carried out on a commercial product, Corsodyl gel^®, in order to compare the drug release control of gel with respect to that of the mucoadhesive tablet, as a formulation for buccal delivery of CHX. While the commercial formulation does not appear to control the release, the formulation containing 15% w/w methocel behaves the best, ensuring the most rapid and complete release of the drug, together with a negligible absorption of the active agent as required for a local antiseptic action in the oral cavity.     

Formulation and Release Kinetics of Sustained Release Phenylpropanolamine Hydrochloride Granules and Tablets

Abstract

Sustained release phenylpropanolamine hydrochloride (PPH) granules and tablets were prepared using HPMC, HPMC and SCMC, Eudragit RS, Eudragit RS+L or HPMC + Eudragit RS matrices. The release pattern of PPH from the prepared granules and tablets was found to be in the following order HPMC > HPMC + SCMC > RS > RS + 1> HPMC + RS. The results revealed that, although the drug concentration was kept constant in all the prepared granules and tablets, the drug release from these formulations was clearly different and depends mainly on the type of matrix used. The presence of Eudragit L with Eudragit RS and Eudragit RS with HPMC resulted in a marked decrease in the drug release compared with that obtained from the matrix containing HPMC or Eudragit RS alone. The release data of PPH from the prepared granules and tablets were treated mathematically according to zero order, first order, Langenbuchar, modified Langenbucher and Higuchi models. The results revealed that no one model was able adequately to describe the drug release profiles from these formulations. In-vivo studies in human volunteers showed that, the peak urinary excretion of PPH occurred over a sustained period from 2 to 6.5 hr in case of HPMC + SCMC tablets and from 2 to 10 hr in case of either RS+L or HPMC + RS tablets.     

Design and Evaluation In Vitro of Controlled Release Mucoadhesive Tablets Containing Chlorhexidine

ABSTRACT

This investigation deals with the development of buccal tablets containing chlorhexidine (CHX), a bis-bis-guanide with antimicrobial and antiseptic effects in the oral cavity, and able to adhere to the buccal mucosa to give local controlled release of drug. A mucoadhesive formulation was designed to swell and form a gel adhering to the mucosa and controlling the drug release into the oral cavity.

Some batches of tablets were developed by direct compression, containing different amounts of hydroxypropylmethylcellulose (HPMC) and carbomer; changing the amount ratio of these excipients in formulations, it is possible easily modulate the mucoadhesive effect and release of drug. The in vitro tests were performed using the USP 26/NF paddle apparatus, a specifically developed apparatus, and a modified Franz diffusion cells apparatus. This last method allows a simultaneous study of drug release rate from the tablets and drug permeation through the buccal mucosa.

Similar tests have also been carried out on a commercial product, Corsodyl gel^®, in order to compare the drug release control of gel with respect to that of the mucoadhesive tablet, as a formulation for buccal delivery of CHX. While the commercial formulation does not appear to control the release, the formulation containing 15% w/w methocel behaves the best, ensuring the most rapid and complete release of the drug, together with a negligible absorption of the active agent as required for a local antiseptic action in the oral cavity.     

Fabrication and in vitro evaluation of bidirectional release and stability studies of mucoadhesive donut-shaped captopril tablets

Objective: To obtain controlled release of captopril in the stomach, coated, mucoadhesive donut-shaped tablets were designed.

Materials and methods: Donut-shaped tablet were made of different ratios of diluents to polymer or combination of polymers by direct compression method. Top and bottom portions of the tablet were coated with water-insoluble polymer followed by mucoadhesive coating. Time of water penetration, measurement of tensile strength, mucoadhesion studies (static ex vivo and ex vivo wash-off) were taken into account for characterization of respective films. In vitro study has been performed at different dissolution mediums. Optimized batches were also prepared by wet granulation. Stability studies of optimized batches have been performed.

Results: The results of time of water penetration and tensile strength indicated positive response against water impermeation. Mucoadhesive studies showed that film thickness of 0.12?mm was good for retention of tablet at stomach. At pH 1.2, optimized batch of tablet made with hydroxypropyl methyl cellulose (HPMC) E15 as binder showed 80% w/w drug release within 4–5?h with maximum average release of 97.49% w/w. Similarly, maximum average releases of 96.36% w/w and 95.47% w/w were obtained with nearly same dissolution patterns using combination of HPMC E5 and HPMC E50 and sodium salt of carboxy methyl cellulose (NaCMC) 500–600 cPs instead of HPMC E15. The release profiles in the distilled water and pH 4.5 followed the above pattern except deviation at pH 6.8. Stability studies were not positive for all combinations.

Conclusion: Coated, mucoadhesive donut-shaped tablet is good for controlled release of drug in the stomach.     

Optimization of piribedil mucoadhesive tablets for efficient therapy of Parkinson’s disease: physical characterization and ex vivo drug permeation through buccal mucosa

Objective: The aim of this study was optimization of buccal piribedil (PR) mucoadhesive tablets to improve its low bioavailability and provide controlled release for the treatment of Parkinson’s disease.

Methods: Buccal tablets were prepared by direct compression method using carbomer (CP), carboxymethyl cellulose (CMC), and hydroxypropyl methylcellulose (HPMC) as mucoadhesive polymers. Physical properties of powder mixtures and buccal tablets were evaluated. Physicochemical compatibility between ingredients was investigated with infrared spectroscopy and differential scanning calorimetry analysis. In vitro dissolution profiles and drug release kinetics of buccal tablets were investigated. Mucoadhesion and ex vivo permeation studies were performed using sheep buccal mucosa.

Results: Powder mixtures demonstrated sufficient flow properties and physical characteristics of all tablet formulations were within compendia limits. Tablet ingredients were absent of any chemical interactions. CP tablets displayed slower drug release compared to HPMC tablets with zero order release, while CMC tablets lost their integrity and released entire drug after 6?h following Higuchi model. All formulations displayed adequate mucoadhesion and steady state flux of PR through buccal mucosa were higher with HPMC compared to CP-containing tablets.

Conclusion: Overall, HPMC was found to combine desired controlled release and mucoadhesion characteristics with sufficient pharmaceutical quality for optimization of buccal tablets. Piribedil mucoadhesive buccal tablets designed for the first time may introduce a new alternative for the treatment of Parkinson’s disease.     

Investigation of the effect of tablet surface area/volume on drug release from hydroxypropylmethylcellulose controlled-release matrix tablets

The purpose of this study was to investigate the influence of tablet surface area/volume (SA/Vol) on drug release from controlled-release matrix tablets containing hydroxypropylmethylcellulose (HPMC). Soluble drugs (promethazine HCl, diphenhydramine HCl, and propranolol HCl) were utilized in this study to give predominantly diffusion-controlled release. Drug release from HPMC matrix tablets with similar values of SA/Vol was comparable within the same tablet shape (i.e., flat-faced round tablets) and among different shapes (i.e., oval, round concave, flat-faced beveled-edge, and flat-faced round tablets). Tablets having the same surface area but different SA/Vol values did not result in similar drug release; tablets with larger SA/Vol values hadfaster release profiles. Utility of SA/Vol to affect drug release was demonstrated by changing drug doses, and altering tablet shape to adjust SA/Vol. When SA/Vol was held constant, similar release profiles were obtained with f2 metric values greater than 70. Thus, surface area/volume is one of the key variables in controlling drug release from HPMC matrix tablets. Proper use of this variable has practical application by formulators who may need to duplicate drug release profiles from tablets of different sizes and different shapes.     

Formulation and in vitro studies of a fixed-dose combination of a bilayer matrix tablet containing metformin HCl as sustained release and glipizide as immediate release

The emerging new fixed dose combination of metformin hydrocholride (HCl) as sustained release and glipizide as immediate release were formulated as a bilayer matrix tablet using hydroxy propyl methyl cellulose (HPMC) as the matrix-forming polymer, and the tablets were evaluated via in vitro studies. Three different grades of HPMC (HPMC K 4M, HPMC K 15M, and HPMC K 100M) were used. All tablet formulations yielded quality matrix preparations with satisfactory tableting properties. In vitro release studies were carried out at a phosphate buffer of pH 6.8 with 0.75% sodium lauryl sulphate w/v using the apparatus I (basket) as described in the United States Pharmacopeia (2000). The release kinetics of metformin were evaluated using the regression coefficient analysis. There was no significant difference in drug release for different viscosity grade of HPMC with the same concentration. Tablet thus formulated provided sustained release of metformin HCl over a period of 8 hours and glipizide as immediate release.     

Formulation and In Vitro Studies of a Fixed-Dose Combination of a Bilayer Matrix Tablet Containing Metformin HCl as Sustained Release and Glipizide as Immediate Release

The emerging new fixed dose combination of metformin hydrocholride (HCl) as sustained release and glipizide as immediate release were formulated as a bilayer matrix tablet using hydroxy propyl methyl cellulose (HPMC) as the matrix-forming polymer, and the tablets were evaluated via in vitro studies. Three different grades of HPMC (HPMC K 4M, HPMC K 15M, and HPMC K 100M) were used. All tablet formulations yielded quality matrix preparations with satisfactory tableting properties. In vitro release studies were carried out at a phosphate buffer of pH 6.8 with 0.75% sodium lauryl sulphate w/v using the apparatus I (basket) as described in the . The release kinetics of metformin were evaluated using the regression coefficient analysis. There was no significant difference in drug release for different viscosity grade of HPMC with the same concentration. Tablet thus formulated provided sustained release of metformin HCl over a period of 8 hours and glipizide as immediate release.     

Oxycellulose as mucoadhesive polymer in buccal tablets

Background: Oxycellulose (OC) is biodegradable and bioabsorbable cellulose derivative used in medicine to support hemostasis and tissue healing. Recently, its antimicrobial and immunomodulating properties, as well as its potential in modern therapeutic systems as release modifying excipient, drug carrier, and/or mucoadhesive polymer, are widely discussed. Method: To study its last-mentioned characteristics, directly compressed tablets containing 5 mg of cetylpyridinium chloride (CPC) as a model drug and 90 mg of mucoadhesive polymer [oxycellulose sodium (NaOC) alone or in a combination with one of five widely used mucoadhesive polymers] were prepared to ensure 8 hours prolonged release of CPC. Physicochemical and mucoadhesive properties of prepared tablets were evaluated. Results: Based on obtained results, tablets containing OC in combination with hydroxypropylmethylcellulose (Methocel® K100LV) or carboxymethylcellulose sodium showed the best quality parameters (friability < 0.04%, tablet thickness < 2.17 mm, tablet hardness > 85 N, residence time > 256 minutes, mucoadhesive strength > 3.45 mN/mm) and dissolution profiles (more than 81% of CPC released within 8 hours). Conclusion: NaOC embodies excellent compressing, mechanical, and mucoadhesive properties; however, formulation with higher content of NaOC only showed shorter adhesion time (107 ± 7 minutes) and faster drug release (93.66% of CPC released within 2 hours), because of its good solubility in aqueous media.     

The influence of HPMC concentration on release of theophylline or hydrocortisone from extended release mini-tablets

Context: Mini-tablets are compact dosage forms, typically 2–3 mm in diameter, which have potential advantages for paediatric drug delivery. Extended release (ER) oral dosage forms are intended to release drugs continuously at rates that are sufficiently controlled to provide periods of prolonged therapeutic action following each administration, and polymers such as hypromelllose (HPMC) are commonly used to produce ER hydrophilic matrices.

Objective: To develop ER mini-tablets of different sizes for paediatric delivery and to study the effects of HPMC concentration, tablet diameter and drug solubility on release rate.

Methods: The solubility of Hydrocortisone and theophylline was determined. Mini-tablets (2 and 3 mm) and tablets (4 and 7 mm) comprising theophylline or hydrocortisone and HPMC (METHOCEL? K15M) at different concentrations (30, 40, 50 and 60%w/w) were formulated. The effect of tablet size, HPMC concentration and drug solubility on release rate and tensile strength was studied.

Results and Discussion: Increasing the HPMC content and tablet diameter resulted in a significant decrease in drug release rate from ER mini-tablets. In addition, tablets and mini-tablets containing theophylline produced faster drug dissolution than those containing hydrocortisone, illustrating the influence of drug solubility on release from ER matrices. The results indicate that different drug release profiles and doses can be obtained by varying the polymer content and mini-tablet diameter, thus allowing dose flexibility to suit paediatric requirements.

Conclusion: This work has demonstrated the feasibility of producing ER mini-tablets to sustain drug release rate, thus allowing dose flexibility for paediatric patients. Drug release rate may be tailored by altering the mini-tablet size or the level of HPMC, without compromising tablet strength.     

Development of amitriptyline buccoadhesive tablets for management of pain in dental procedures

Administration of lidocaine and nonsteroidal anti-inflammatory drugs (NSAIDs) as a routine procedure for relief of dental pains by and large is restricted due to some side effects. Amitriptyline (AM) has long been known to exert analgesic activity as a result of blocking the Na? channels. The objective of the present investigation was to prepare suitable buccoadhesive tablets using cellulose derivatives in order to obtain new formulations containing AM to provide local analgesic action. The tablets were evaluated in terms of physical characteristics, mucoadhesion performance, drug release, and in vivo assessment of analgesic efficiency. Tablets containing higher amounts of high-viscosity hydroxypropylmethyl cellulose (HPMC-K4M) significantly demonstrated enhanced adhesive performances. On the other hand, presence of sodium carboxymethyl cellulose (NaCMC) in formulations including HPMC of lower-viscosity grade (HPMC-E5LV) provided further adhesiveness by increase in viscosity. Rate of drug release from HPMC-E5LV tablets was significantly higher than the HPMC-K4M tablets. Kinetically, patterns of AM release from the tablets fitted best to Higuchi model. Moreover, in a randomized double-blind trial, analgesic efficiency of the prepared bioadhesive tablets was revealed to be satisfactory. It is suggested that applying the topical AM mucoadhesive tablet containing the low amount of drug is a safe and promising alternative to relief the pain in the buccal region.     

Release Kinetics and Availability of Mebeverine Hydrochloride from Polycarbophil Loaded by Swelling

The release rate and mechanism of release of mebeverine hydrochloride were studied for commercial “Duspatalin” tablets and for different tablet formulations (F₁, F₂ & F₃) containing 20, 40 and 65% polycarbophil, respectively. The formulated granules were obtained by freeze drying of polycarbophil granules loaded with aqueous solution of the drug at 25°C by swelling of the polymer. The release of mebeverine hydrochloride from prepared tablet formulations was faster than that of Duspatalin tablets. The release rate of the drug increased as the polycarbophil content of the tablets increased. The calculated correlation coefficients for the release data fitted to various models showed that the release from Duspatalin tablets and F₂ follow first order kinetics, while release of F₁ approaches that of zero order. The release mechanism from F₃ could not be determined. DSC thermograms showed that there is an interaction between the drug and the polymer in aqueous medium, but not in the solid state.

The in-vivo guinea-pig studies revealed that mebeverine hydrochloride was released and absorbed from the tested formula (F₃), depressed the agonists-induced contractions 2 hrs after treatment but not after 4 hrs indicating rapid absorption and metabolism. The percentage inhibitions ranged from 40–85%. The treatment seems to antagonise barium chloride (BaCl₂)-induced contractions more than those induced by carbochol.     

In vitro and in vivo adhesion testing of mucoadhesive drug delivery systems

Bioadhesive tablets were prepared by physical mixing of polymers and drug, then granulating and compressing into a tablet. The mucoadhesion was evaluated by shear stress measurement, detachment force measurement, and X-ray photography of the rabbit gastrointestinal tract. The strong interaction between the polymer and the mucous lining of the tissue helps increase contact time and permit localization. Polymers like hydroxypropyl methylcellulose K4M (HPMC K4M), hydroxypropyl methylcellulose 100 cps (HPMC 100 cps), carbopol-934, sodium carboxy methylcellulose (Na CMC), guar gum, and polyvinylpyrrolidone (PVP) were tested by shear stress measurement and detachment force measurement methods. HPMC K4M, showing maximum bioadhesion, was used in further studies. Adhesion was maximum between pH 5 and pH 6. Maximum adhesion was observed in the duodenum, followed by the jejunum and ileum. Barium sulfate (BaSO₄) matrix tablets containing polymer and drug were subjected to X-ray studies in rabbits, and it was found that the tablet was mucoadhesive even after 8 hr. Enteric coating did not show any effect on mucoadhesion after passing from the stomach.     

Sustained Release from Precirol® (Glycerol Palmito-Stearate) Matrix. Effect of Mannitol and Hydroxypropyl Methylcellulose on the Release of Theophylline

The release of theophylline embedded in a Precirol® (glycerol palmitostearate) matrix containing varying amounts of mannitol and/or hydroxypropyl methyl cellulose 4000 (HPMC) was studied. The results indicated that HPMC or mannitol when incorporated alone, the drug release followed the diffusion-controlled matrix model where the quantity of drug released was proportional to the square root of time. The release rate was found to increase with increase in the amount of HPMC or mannitol in the matrix. When both mannitol and HPMC were incorporated in the matrix, the mechanism of release changed from the Higuchi model to a first-order release. A linear relationship was found between the fraction of HPMC or mannitol in the matrix and the rate constant. An optimum combination of Precirol®, mannitol and HPMC was found for a 12 hour theophyll ine sustained release preparation     

Studies on the Delivery Mechanisms of Theophylline from a Sustained Release Tablet

The in-vitro and in-vivo release of theophylline from an oral sustained release tablet (Theograd^R) was studied.

The in-vitro release profiles were determined by means of the rotating basket method, the paddle method and the modified disintegration method, described in the USP XX as apparatus 1, 2 and 3 respectively. Besides a stationary basket-rotating paddle method was used.

It was demonstrated that in the stationary basket-rotating paddle apparatus and in the paddle apparatus at low rotational speeds of the paddle, mild agitation conditions were created. Under these conditions the release of theophylline from the sustained release tablet appeared to be matrix controlled. The leached matrix was found to be structurally very weak. For a matrix type of sustained release tablet this is probably beneficial as it would be less likely to cause accumulation and gastro-intestinal obstruction. In contrast the conditions of agitation in the rotating basket apparatus and in the disintegration apparatus were found to be rather severe. This was partly due to mechanical abrasion of the dosage form caused by the gauze of the basket and the basket-rack respectively, and partly the result of high solvent agitation, especially in the disintegration apparatus. Under these conditions it appeared that the empty matrix of the sustained release tablet eroded during the release process. This was confirmed by the results of studies under non-dissolving circumstances of the drug which showed that in this case only the leached matrix of the sustained release dosage form eroded and not that part of the dosage form from which the drug had not yet been dissolved. The in-vivo absorption appears to relate to the in-vitro release. When the Theograd tablet was taken on an empty stomach, it appeared that the absorption rate could succesfully be simulated by means of the stationary basket-rotating paddle method and the paddle method, both at low rotational speeds of the paddle. It was very likely that in this case the in-vivo release from the sustained release tablet was matrix controlled too. Under these conditions the bioavailability was found to be 65% compared with an oral solution of the drug. In contrast, when the Theograd tablet was taken after a meal, a relative bioavailability of 90% was observed. It was made plausible, that the greatly enhanced bioavailability, observed on postprandial administration of the tablet, was due to partial erosion of the leached matrix. This erosion was caused by the food induced increased motility of the gastro-intestinal tract. Based on the results of this study it is recommended to take Theograd^R tablets after a meal.     

The effects of PH, Ionic concentration and ionic species of dissolution media on the release rates of quinidine gluconate sustained release dosage forms

The dissolution profiles of some extended release quinidine gluconate products were shown to be dependent on several dissolution medium variables. It was shown that, for a quinidine gluconate wax matrix tablet, the dissolution rate has an unexpected inverse relationship to the solubility as a function of pH. The dissolution rate is also affected by the concentration of chloride ion present in the dissolution medium apparently due to the inhibition of disintegration. It was found that the nature of the anion (inorganic vs. organic) of the dissolution buffer plays a significant role in the release of the drug. Salts of inorganic acids used as part of the buffer system lower the rate of release of quinidine gluconate from wax matrix tablets through an inhibition of disintegration. On the other hand, buffer salts of organic acids do not have any appreciable effect on the disintegration or dissolution of these tablets. Since the concentration of chloride ion in both gastric and intestinal juices is approximately 0.1M, this suggests that the use of a dissolution medium containing chloride ion represents the more appropriate approach when an in-vivo/in-vitro correlation is desired. For all the quinidine gluconate controlled release formulations studied, mechanisms of release are of at least two different types. This makes the selection of a single dissolution medium for in-vivo/in-vitro correlations either improbable or impossible.     

Effect of Excipient and Processing Variables on Adhesive Properties and Release Profile of Pentoxifylline From Mucoadhesive Tablets

ABSTRACT

The bioavailability and onset of action of drugs with high first-pass metabolism can be significantly improved by administration via the sublingual route. The objective of this study was to evaluate the effect of polymer type and tablet compaction parameters on the adhesive properties and drug release profile from mucoadhesive sublingual tablet formulations. Pentoxifylline was selected as the model drug because it has poor oral bioavailability due to extensive first-pass metabolism. Two polymers known to possess mucoadhesive properties, carbomer and hydroxypropyl methyl cellulose (HPMC), were used to prepare the formulations. Tablets were prepared by using direct compression technique and evaluated for in vitro dissolution, drug-excipient interactions, and adhesive properties. In general, there was a decrease in the rate of drug release with an increase in the concentration of polymers. No drug-excipient interactions were evident from differential scanning calorimetry or high-performance liquid chromatography analysis. For the formulations containing HPMC, the force of mucoadhesion increased with an increase in the concentration of polymer; however, for carbomer formulations, no such correlation was observed. Force of mucoadhesion decreased as a function of hydration time in both of the polymers.     

Does the performance of wet granulation and tablet hardness affect the drug dissolution profile of carvedilol in matrix tablets?

Wet granulation is mostly used process for manufacturing matrix tablets. Compared to the direct compression method, it allows for a better flow and compressibility properties of compression mixtures. Granulation, including process parameters and tableting, can influence critical quality attributes (CQAs) of hydrophilic matrix tablets. One of the most important CQAs is the drug release profile. We studied the influence of granulation process parameters (type of nozzle and water quantity used as granulation liquid) and tablet hardness on the drug release profile. Matrix tablets contained HPMC K4M hydrophilic matrix former and carvedilol as a model drug. The influence of selected HPMC characteristics on the drug release profile was also evaluated using two additional HPMC batches. For statistical evaluation, partial least square (PLS) models were generated for each time point of the drug release profile using the same number of latent factors. In this way, it was possible to evaluate how the importance of factors influencing drug dissolution changes in dependence on time throughout the drug release profile. The results of statistical evaluation show that the granulation process parameters (granulation liquid quantity and type of nozzle) and tablet hardness significantly influence the release profile. On the other hand, the influence of HPMC characteristics is negligible in comparison to the other factors studied. Using a higher granulation liquid quantity and the standard nozzle type results in larger granules with a higher density and lower porosity, which leads to a slower drug release profile. Lower tablet hardness also slows down the release profile.