In vivo bioavailability studies of sumatriptan succinate buccal tablets

Back ground and the purpose of study

Sumatriptan succinate is a Serotonin 5- HT1 receptor agonist, used in treatment of migraine. It is absorbed rapidly but incompletely when given orally and undergoes first-pass metabolism, resulting in a low absolute bioavailability of about 15%. The aim of this work was to design mucoadhesive bilayered buccal tablets of sumatriptan succinate to improve its bioavailability.

Methods

Mucoadhesive polymers carbopol 934 (Carbopol), HPMC K4M, HPMC K15M along with ethyl cellulose as an impermeable backing layer were used for the preparation of mucoadhesive bilayered tablets. In vivo bioavailability studies was also conducted in rabbits for optimized formulation using oral solution of sumatriptan succinate as standard.

Results

Bilayered buccal tablets (BBT) containing the mixture of Carbopol and HPMC K4M in the ratio 1:1 (T1) had the maximum percentage of in vitro drug release within 6 hrs. The optimized formulation (T1) followed non-Fickian release mechanism. The percentage relative bioavailability of sumatriptan succinate from selected bilayered buccal tablets (T1) was found to be 140.78%.

Conclusions

Bilayered buccal tablets of sumatriptan succinate was successfully prepared with improved bioavailability.     

Preparation and Evaluation of Buccoadhesive Films of Atenolol

This paper describes the preparation of new bilayered device comprising a drug containing mucoadhesive layer and a drug free backing layer. Bilaminated films were produced by a casting/ solvent evaporation technique. The mucoadhesive layer was composed of mixture of drug and sodium alginate with or without carbopol 934 P, and backing layer was made of ethyl cellulose. The double layer structure design was expected to provide drug delivery in a unidirectional fashion to the mucosa and avoid loss of drug due to wash out with saliva. The fabricated films were subjected to in vitro drug release, in vitro permeation through porcine buccal mucosa. The bilayered films were also evaluated for mucoadhesive strength, mucoadhesive time, folding endurance, hydration studies and tensile strength.     

Mucoadhesive bilayer buccal tablet of carvedilol-loaded chitosan microspheres: in vitro,pharmacokinetic and pharmacodynamic investigations

A multiple-unit system comprising mucoadhesive bilayer buccal tablets of carvedilol-loaded chitosan microspheres (CMs) was developed to improve bioavailability and therapeutic efficacy of carvedilol. Drug-loaded CMs were prepared by spray drying, evaluated for powder and particle characteristics, and optimized batch of CMs was compressed into bilayer buccal tablets using Carbopol. Tablets were evaluated for physicochemical parameters, in vitro drug release, in vivo pharmacokinetic and pharmacodynamic studies. Optimized formulation, CMT1 (CMT, chitosan microsphere tablet) showed maximum mucoadhesive force (50?±?1.84?dyne/cm²), exhibited 73.08?±?3.05% drug release and demonstrated zero-order kinetics with non-Fickian release mechanism. Pharmacokinetic studies in rabbits showed significantly higher C_max (71.26?±?6.45?ng/mL), AUC_0–10 (AUC, area under the curve 390.75?±?5.23?ng/mL/h) and AUC_0–∞ (664.72?ng/mL/h) than carvedilol oral tablet. Pharmacodynamic studies confirmed reduction in mean arterial pressure, heart rate, body weight and triglyceride on administration of bilayer buccal tablet compared to oral carvedilol tablet. Multiple-unit system exhibited enhanced bioavailability and sustained release of carvedilol, indicating its improved therapeutic potential for the treatment of hypertension.     

Development and in vivo evaluation of buccal tablets prepared using danazol-sulfobutylether 7 beta-cyclodextrin (SBE 7) complexes

The aim of the present work was to develop a mucoadhesive controlled-release formulation of danazol-sulfobutylether 7 beta-cyclodextrin (SBE 7) complex and to evaluate the feasibility of improving the bioavailability of danazol via the buccal route. Different types of polymers, polycarbophil (PC) and hydroxypropylmethyl cellulose (HPMC) were mixed with danazol-SBE 7 complex and compressed into tablets. These tablets were evaluated for their dissolution and mucoadhesion properties and for drug absorption in female beagle dogs. Increased mucoadhesion was observed for PC-containing tablets compared with HPMC tablets. As the concentration of polymer increased, drug release decreased, and PC-containing tablets gave slower release compared to HPMC tablets. In vivo bioavailability performed in dogs showed that the perorally administered danazol-SBE 7 complex and the danazol-SBE 7 (in PC matrix) buccal tablets had absolute bioavailabilities of 64% and 25%, respectively, that are significantly greater than 1.8% observed for the commercial formulation Danocrine. The increased bioavailability was attributed to the enhanced solubility consequent to complexation, and the possible avoidance of first-pass metabolism upon buccal administration.     

Mucoadhesive buccal film containing ornidazole and dexamethasone for oral ulcers: in vitro and in vivo studies

A bilayered mucoadhesive buccal film containing a combination of ornidazole (OD) and dexamethasone sodium phosphate (DEX) was prepared using solvent casting to treat oral ulcers. Films were systematically evaluated in vitro to obtain the optimum formulation. The therapeutic effects of these films were investigated in the rabbit oral ulcer model and the in vivo release of OD and DEX in the human oral cavity was also evaluated. The backing layer contained ethyl cellulose and an optimal mucoadhesive layer containing both OD and DEX was produced. Films from the optimum formulation were 0.427?±?0.015?mm thick, weighed 55.89?±?0.79?mg, and had a surface pH of 6.34?±?0.01. The drug content of the optimum formulation approximated the theoretical value with good uniformity (2.959?±?0.106?mg/cm² for OD and 0.877?±?0.031?mg/cm² for DEX). The formulation showed favorable swelling characteristics and both drugs were released at >95% after 4?h. Moreover, the compound film had a statistically significant effect on mucosal repair and reduced ulcer inflammation without stimulating the human oral mucosa. C_max of OD in saliva was 37.04?μg/ml and that of DEX was 9.737?μg/ml. Given promising therapeutic effects, the compound film developed here could become a local drug delivery device for treating oral ulcers.     

Badam gum: a natural polymer in mucoadhesive drug delivery. Design,optimization, and biopharmaceutical evaluation of badam gum-based metoprolol succinate buccoadhesive tablets

Context: Applicability of natural polymers in pharmaceutical drug delivery.

Objective: The objective of the present investigation was to evaluate the applicability of badam gum (BG) obtained from Terminalia catappa LINN, belongs to the family combretaceae as a buccoadhesive polymer using metoprolol succinate as a model drug.

Methods: Tablets were prepared by wet granulation technique. Compression coating technique was employed for the preparation of unidirectional release buccal tablets using cellulose acetate as an impermeable backing layer.

Results: Muco/buccoadhesive properties of the BG were increased with the increase in the concentration of polymer which was evident form the detachment force measurement, ex vivo residence time, and swelling studies. MBG 2 was found to be the optimized formulation based on drug dissolution studies and bioadhesion studies. FTIR and DSC studies performed on the optimized formulation indicated no drug–polymer interaction. MBG 2 was found to be stable after accelerated stability testing for 6 months as per ICH guidelines. Pharmacokinetic studies of the optimized formulation were performed in six healthy human volunteers in comparison with that of the commercial extended release oral tablet GUDPRESS XL-25 by estimating pharmacokinetic parameters and mean residence time (MRT). It was found that there is a significant increase in the bioavailability of metoprolol succinate from BG formulation which was evident from the high AUC and MRT values compared with the commercial formulation.

Conclusion: The above results clearly indicated that badam gum can be used as a mucoadhesive polymer for buccal drug delivery.     

Nanotransfersomes-loaded thermosensitive in situ gel as a rectal delivery system of tizanidine HCl: preparation,in vitro and in vivo performance

The purpose of the current study was to develop tizanidine HCl (TIZ; a myotonolytic agent used for treatment of spasticity) loaded nanotransfersomes intended for rectal administration, aiming to bypass the hepatic first-pass metabolism. TIZ-loaded nanotransfersomes were prepared by thin-film hydration method followed by characterization for various parameters including entrapment efficiency, vesicle diameter, in vitro release and ex vivo permeation studies. Transfersomal formulation composed of phosphatidylcholine and Tween 80 at a weight ratio of (85:15) gave a satisfactory results. It exhibited encapsulation efficiency of 52.39%, mean diameter of 150.33?nm, controlled drug release over 8?h and good permeation characteristics. Optimum formula was then incorporated into Pluronic-based thermoreversible gel using hydroxypropyl methylcellulose (HPMC) as a mucoadhesive polymer. Pharmacokinetic study was performed by rectal administration of transfersomes-loaded in situ gel to rabbits and compared with oral drug solution and rectal TIZ in situ gel. The pharmacokinetic study revealed that the transfersomal formulation successively enhanced the bioavailability of TIZ by about 2.18-fold and increased t_1/2 to about 10?h as compared to oral solution. It can be concluded that encapsulation of TIZ into nanotransfersomes can achieve a dual purpose of prolonged TIZ release and enhanced bioavailability and so may be considered as a promising drug delivery system for the treatment of spasticity.     

Development of mucoadhesive patches for buccal administration of carvedilol

A buccal patch for systemic administration of carvedilol in the oral cavity has been developed using two different mucoadhesive polymers. The formulations were tested for in vitro drug permeation studies, buccal absorption test, in vitro release studies, moisture absorption studies and in vitro bioadhesion studies. The physicochemical interactions between carvedilol and polymers were investigated by Fourier transform infrared (FTIR) Spectroscopy. According to FTIR the drug did not show any evidence of an interaction with the polymers used and was present in an unchanged state. XRD studies reveal that the drug is in crystalline state in the polymer matrix. The results indicate that suitable bioadhesive buccal patches with desired permeability could be prepared. Bioavailability studies in healthy pigs reveal that carvedilol has got good buccal absorption. The bioavailability of carvedilol from buccal patches has increased 2.29 folds when compared to that of oral solution. The formulation AC5 (HPMC E 15) shows 84.85 + 0.089% release and 38.69 + 6.61% permeated through porcine buccal membrane in 4 hr. The basic pharmacokinetic parameters like the C(max), T(max) and AUC(total) were calculated and showed statistically significant difference (P<0.05) when given by buccal route compared to that of oral solution.     

Buccal administration of mucoadhesive blend films saturated with propranolol loaded nanoparticles

The aims of this study were to prepare and characterize hydroxypropyl methylcellulose (HPMC)/polycarbophil (PC) mucoadhesive blend films saturated with propranolol hydrochloride (PNL)-loaded nanoparticles to improve permeability of drugs that undergo first-pass metabolism. An ionic cross-linking method and film casting technique was used to prepare nanoparticles and mucoadhesive blend films, respectively. Increasing concentrations of PNL (70, 80, 90 mg/film) in HPMC/PC blend films containing PNL-loaded nanoparticles (PN-films) and HPMC/PC blend films containing PNL (80 mg/film) without nanoparticles (PP-films) were prepared to test swelling, mucoadhesiveness, release, permeation and physicochemical properties. Scanning electron microscope (SEM) images showed a partially smooth surface with a wrinkled occurrence and spherically shaped, well-dispersed nanoparticles on the surface of PN-films containing PNL 80 mg/film (PN-films-80). The size of the nanoparticles on the surface of PN-films-80 was around 100 nm, which was similar to the nanoparticle size observed using light scattering technique. The swelling index (SI) of all PN-films and PP-films increased greatly in the first period time (10–20 min) and reached swelling equilibrium at 20 min and 30 min, respectively. For the PN-films, the concentration of PNL influenced the mucoadhesive properties and tended to be higher when the amount of PNL increased. Immediate release of all blend film formulations was found in early time points (10–30 min). After 120 min, the release of PN-films-70 was lower than the other PN-films. Permeation studies using porcine buccal mucosa showed that inclusion of nanoparticles in the films increased the permeability of PNL compared to PP-films. Therefore, buccal administration of mucoadhesive blend films containing PNL-loaded nanoparticles could be a promising approach for drugs that undergo first-pass metabolism.     

Development of mucoadhesive buccal films for the treatment of oral sub-mucous fibrosis: a preliminary study

The objective of the present study was to develop the mucoadhesive buccal film of valdecoxib for the treatment of oral sub mucous fibrosis, a localized buccal disease. Valdecoxib, a novel COX-2 inhibitor has been reported to be used in various osteopathic and rheumatoid conditions as oral therapy. The films were made out of chitosan and HPMC K4M as polymers. Sodium taurocholate was used as a permeation enhancer. All the formulations were examined for film thickness, swelling properties, drug content, weight variation, in vitro release studies, bioadhesive force, tensile strength, diffusion studies using pig mucosa and pharmacokinetic study in healthy male volunteers. Prepared films were thin, flexible, smooth and transparent. Bioadhesive force and tensile strength of the optimized formulation were found to be 75 ± 4 kg m^?1 S^?2 and more than 2.5 kg/3 cm², respectively. The percent drug content was 98.5 ± 1.3%. The in vitro drug release from the selected formulation showed that about 69.34% of the drug payload was released up to 6 hours. The drug permeation through the dialysis sac and pig buccal mucosa was found to be 62.70% and 54.39%, respectively. Pharmacokinetic studies of the buccal mucoadhesive film showed that the drug was released locally at the target site of action, and a very small amount might have absorbed systemically.     

Development and in vitro evaluation of buccoadhesive carvedilol tablets

Buccoadhesive tablets of carvedilol were prepared using HPMC K4M, HPMC K15M and Carbopol 934 as mucoadhesive polymers. Fifteen formulations were developed with varying concentrations of polymers. Formulations of the BC or BD series were composed of HPMC K4M or HPMC K15M in ratios of 1:1 to 1:5 whereas in the BE series Carbopol 934 was used (1:0.25 to 1:1.50). The formulations were tested for in vitro drug release, in vitro bioadhesion, moisture absorption and in vitro drug permeation through porcine buccal mucosa. Formulation BC3 showed maximum release of the drug (88.7 +/- 0.4%) with the Higuchi model release profile and permeated 21.5 +/- 2.9% of the drug (flux 8.35 +/- 0.291 microg h(-1)cm(-2)) permeation coefficient 1.34 +/- 0.05 cm h(-1)) through porcine buccal membrane. BC3 formulation showed 1.62 +/- 0.15 N of peak detachment force and 0.24 +/- 0.11 mJ of work of adhesion. FTIR results showed no evidence of interaction between the drug and polymers. XRD study revealed that the drug is in crystalline form in the polymer matrix. The results indicate that suitable bioadhesive buccal tablets with desired permeability could be prepared.     

Bilayered transmucosal drug delivery system of pravastatin sodium: statistical optimization, in vitro, ex vivo, in vivo and stability assessment

The objective of the present study was to develop a mucoadhesive sustained release bilayered buccal patch of pravastatin sodium using Eudragit S100 as the base matrix so as to surmount hepatic first pass metabolism and gastric instability of the drug. A 32 full factorial design was employed to study the effect of independent variables viz. levels of HPMC K4M and carbopol 934P on % cumulative drug release, mucoadhesion time and mucoadhesive force. Amount of carbopol 934P and HPMC K4M significantly influenced characteristics like swelling index, in vitro mucoadhesive force, drug release, and mucoadhesion time. In vitro evaluation revealed that formulations exhibited satisfactory technological parameters. The mechanism of drug release was found to be non-Fickian diffusion. Different permeation enhancers were investigated to improve the permeation of drug from the optimized patches (F9) across the buccal mucosa. Formulation [F9 (P3)] containing 4% (v/v) dimethyl sulfoxide exhibited desirable permeation of drug. Histopathological studies performed using goat buccal mucosa revealed no mucosal damage. Bioavailability studies in rabbits demonstrated that [F9 (P3)] significantly higher C(max) (67.34?±?3.58?ng/ml) and AUC??∞ (350.27?±?9.59?ng/ml×h) (p < 0.05) of pravastatin sodium from optimized patch than IR tablet (C(max) 58.73?±?4.63?ng/ml and AUC??∞ 133.80?±?8.25?ng/ml×h). Formulation [F9 (P3)] showed sustained drug plasma concentration over a period of 10?h which was significantly longer than oral tablet (p < 0.05). Stability studies as per ICH guidelines established physical stability of the patch and chemical stability drug. The present study established potential of the optimized mucoadhesive buccal patches to circumvent the hepatic first-pass metabolism, gastric instability and to improve bioavailability of pravastatin sodium.     

Formulation development and optimization of bilayer tablets of aceclofenac

Objective: The objective of the present study was to develop bilayer tablets of aceclofenac that are characterized by initial burst drug release followed by sustained release of drug.

Methods: The fast-release layer of the bilayer tablet was formulated using microcrystaline cellulose (MCC) and HPMC K4M. The amount of HPMC E4M (X₁) and MCC (X₂) was used as independent variables for optimization of sustained release formulation applying 3² factorial design. Three dependent variables were considered: percentage of aceclofenac release at 1 h, percentage of aceclofenac release at 12 h, and time to release 50% of drug (t_50%). The composition of optimum formulation of sustained release tablets were employed to formulate double layer tablets.

Results: The results indicate that X₁ and X₂ significantly affected the release properties of aceclofenac from sustained release formulation. The double layer tablets containing fast-release layer showed an initial burst drug release of more than 30% of its drug content during first 1 h followed by sustained release of the drug for a period of 24 h.

Conclusion: The double layer tablets for aceclofenac can be successfully employed as once-a-day oral-controlled release drug delivery system characterized by initial burst release of aceclofenac for providing the loading dose of drug.     

Buccal films of prednisolone with enhanced bioavailability

Abstract

The conventional formulation of prednisolone is considered to be low in efficacy, primarily on account of their failure in providing and maintaining effective therapeutic drug levels. This study aims to focus on development of a mucoadhesive buccal delivery system with a twofold objective of offering a rapid as well as a prolonged delivery of prednisolone coupled with enhanced therapeutic efficacy. Buccoadhesive films of prednisolone were prepared by solvent-casting method using hydroxyl propyl methyl cellulose (K100), Carbopol 940 and/or Eudragit® NE 40?D. Placebo films possessing the most desirable physicomechanical properties were selected for drug loading. The effect of polymer and its content on film properties, i.e. mucoadhesive strength, swelling and hydration, in vitro drug release was studied. Based on these studies, film F7D was selected for ex vivo permeation across porcine cheek mucosa. The steady state flux of prednisolone across the buccal mucosa was found to be 105.33?±?32.07?µg/cm²/h. A comparative pharmacokinetic study of prepared film (F7D) and oral suspension of prednisolone was conducted. In vivo data of buccal film show greater bioavailability (AUC_0–α: 24.26?±?4.06?µg.h/ml versus 10.65?±?2.15?µg.h/ml) and higher C_max (2.70?±?0.38?µg/ml versus 2.29?±?0.32?µg/ml) value when compared to oral suspension. The data observed from this study highlight the feasibility of the buccal route as a viable option for delivery of prednisolone.     

Design and evaluation of ondansetron liquid suppository for the treatment of emesis

The thermosensitive–mucoadhesive ondansetron liquid suppository (tmOLS) was developed to enhance patient compliance and bioavailability in high-risk patients receiving highly emetogenic therapy and having difficulty in swallowing, The thermosensitive–mucoadhesive liquid suppository bases were formulated using poloxamers (P407 and P188) and hydroxypropylmethyl cellulose (HPMC). The physicochemical properties of the liquid suppository bases were characterized by their gelation temperature, mucoadhesive force, rheological properties, and in vitro release. Rectal mucosal damage following rectal administration of tmOLS in rats was assessed using microscopy. Pharmacokinetic analyses were performed to compare tmOLS administered via the rectal route to ondansetron solution administered orally. The liquid suppository base of tmOLS contained P407, P188, and HPMC in the ratio 18:20:0.8, was in the liquid state at room temperature, underwent gelation at body temperature. Area under the curve and half-life (t_1/2) of ondansetron were significantly higher in the tmOLS-treated group, indicating that the formulation bypassed the first-pass metabolism and that it was released slowly from the tmOLS because of the formation of mucoadhesive gel state. Furthermore, the t_1/2 of tmOLS was two-fold that of the oral solution. Thus, tmOLS could be administered to patients who have difficulty in swallowing; however, adjustments in dosing interval may be needed.     

Mucoadhesive buccal films containing phospholipid-bile salts-mixed micelles as an effective carrier for Cucurbitacin B delivery

Abstract

Cucurbitacin B (Cu B), a potent anti-cancer agent, suffers with the problems of water-insoluble, gastrointestinal side effects and non-specific toxicity via oral administration and drawbacks in patient’s compliance and acceptance through injections. An integration of nanoscale carriers with mucoadhesive buccal films drug delivery system would resolve these issues effectively with greater therapeutic benefits and clinical significance. Thus, the drug loaded mucoadhesive buccal film was developed and characterized in this study and the carboxymethyl chitosan (CCS) was chosen as a bioadhesive polymer, glycerol was chosen as a plasticizer and phospholipid-bile salts-mixed micelles (PL-BS-MMs) was selected as the nanoscale carriers. The CCS-films containing Cu B loaded PL-SDC-MMs was evaluated for the mechanical properties, mucoadhesion properties, in vitro water-uptake, in vitro release and morphological properties, respectively. The optimal CCS-films containing Cu B loaded PL-SDC-MMs was easily reconstituted in a transparent and clear solution with spherical micelles in the submicron range. The in vivo study revealed a greater and more extended release of Cu B from nanoscale CCS-films compared to that from a conventional CCS films (C-CCS-films) and oral marketed tablet (Hulusupian). The absorption of Cu B from CCS-films containing Cu B loaded PL-SDC-MMs resulted in 2.69-fold increased in bioavailability as compared to conventional tablet formulation and 10.46 times with reference to the C-CCS-films formulation. Thus, this kind of mucoadhesive buccal film might be an alternative safe route for delivery of Cu B with better patient compliance and higher bioavailability for the treatments.     

Development of three layered buccal compact containing metoprolol tartrate by statistical optimization technique

The objective of this work to evaluate the effect of formulation variables on release properties and bioadhesive strength in development of three layered buccal compact containing highly water-soluble drug metoprolol tartrate (MT) by statistical optimization technique. Formulations were prepared based on rotatable central composite design with peripheral polymer ratio (carbopol 934P: HPMC 4KM) and core polymer ratio (HPMC 4KM: sodium alginate) as two independent formulation variables. The three layered buccal compact comprises a peripheral layer, core layer and backing layer. Four dependent (response) variables were considered: bioadhesion force, percentage MT release at 8 h, T50% (time taken to release 50% of drug) and release exponent (n). The release profile data was subjected to curve fitting analysis for describing the release mechanism of MT from three layered buccal compact. The main effects and interaction terms was quantitatively evaluated by quadratic model. The decrease in MT release was observed with an increase in both the formulation variables and as the carbopol: HPMC ratio increases the bioadhesive strength also increases. The desirability function was used to optimize the response variables, each having a different target and the observed responses were highly agreed with experimental values. The results demonstrate the feasibility of the model in the development of three layered buccal compact containing highly water-soluble drug MT.     

Development and In vitro Evaluation of Mucoadhesive Buccal Films of Nebivolol

Nebivolol, a cardioselective β-blocker undergoes extensive metabolism in the liver after its oral administration resulting in low bioavailability. Oral administration of nebivolol also causes gastrointestinal disturbances characterised by stomach ache. To overcome these short comings, mucoadhesive buccal films of nebivolol were prepared using different concentrations of hydroxypropyl methylcellulose and hydroxyl ethylcellulose in the ratios of 2:1, 4:1 and 6:1 and hydroxypropyl methylcellulose and methylcellulose in the ratio of 2:2, 4:3 and 6:4 by solvent casting technique. All the prepared films were found to be smooth, elegant and uniform in thickness and weight. Among the three polymer combinations used, 6:4 (BFN₆) showed increased in vitro residence time, which appeared to be mainly due to mucoadhesive nature of hydroxylpropyl methylcellulose and methylcellulose. Evaluation of the films showed uniform dispersion of the drug throughout the formulation (96.21±0.71 to 97.02±0.12%). In vitro drug release studies showed better results at the end of 8 h. The release profile of all the formulations was subjected to kinetic analyses, which suggested that the drug was released by diffusion mechanism following super case-II transport.     

A novel tri-layered buccal mucoadhesive patch for drug delivery: assessment of nicotine delivery

Objectives The aim of this study was to assess the potential of a novel delivery device for administering drugs that suffer from a high degree of first‐pass metabolism. Methods A tri‐layered buccal mucoadhesive patch, comprising a medicated dry tablet adhered to a mucoadhesive film, was prepared and characterized by its physicochemical properties and mucoadhesive strength. Nicotine was used as a model drug for the characterization of drug release and drug permeation. The influence of different adsorbents on the release of nicotine base from the patches was evaluated in vitro. Different molecular forms of nicotine (base and complex salt) were evaluated for their effect on release performance and permeation in vitro. Key findings Results demonstrated acceptable physicochemical and mucoadhesive properties for the tri‐layered patch. Rapid release of nicotine was observed when nicotine base was incorporated with calcium sulfate dihydrate as the adsorbent. Patches incorporating nicotine base showed distinct advantages over those containing nicotine polacrilex, in terms of drug release (complete drug release achieved at 30 vs 60 min) and transmucosal permeation (37.28 ± 4.25 vs 2.87 ± 0.26% of the dose permeating through mucosa within 120 min). Conclusions The novel tri‐layered patch can effectively adhere to, and deliver an active ingredient through the buccal mucosa, confirming its potential for buccal mucoadhesive drug delivery.     

Formulation development of Carvedilol compression coated tablet

Purpose: The aim of present research was to produce carvedilol compression coated tablet to provide biphasic drug release.

Method: A compressed coated tablet made of a sustained release core tablet and an immediate release coat tablet. Both the core and the coat contained carvedilol. The sustained release effect was achieved with polymers (HPMC K₄M and PEO WSR 205) to modulate the release of the drug. The powder blends for core and coat tablets were evaluated for angle of repose, bulk density, compressibility index, and drug content. Compressed coated tablets were evaluated for thickness, diameter, weight variation test, drug content, hardness, friability, disintegration and in vitro release studies.

Result: The powder blends showed satisfactory flow properties, compressibility, drug content and all the tablet formulations showed acceptable pharmaco-technical properties. Carvedilol contained in the fast releasing component was released within 3?min, whereas the drug in the core tablet was released at different times up to 24?h, depending on the composition of the matrix tablet. The mechanism of drug release was fickian diffusion or anomalous behavior.

Discussion: Batch F7, containing 10?mg PEO WSR 205 and 5?mg HPMC K₄M, showed maximum similarity with theoretical profile and zero order drug release kinetic.