Pharmaceutical and pharmacokinetic evaluation of a newly formulated multiparticulate matrix of levodopa and carbidopa.

Levodopa is routinely co-administered with carbidopa in the management of Parkinson's disease. Although the aforementioned combination therapy is effective, there may be fluctuating plasma levels of levodopa after oral administration. We formulated and evaluated the kinetic characteristics of the chitosan-pectin-based multiparticulate matrix of levodopa and carbidopa. Pectin was extracted from the cocoa husk, and the chitosan-pectin-based matrix was prepared by wet granulation. Formulations were evaluated for drug-excipient compatibility, drug content, precompression properties and in vitro release. For pharmacokinetic evaluation, rats were put into groups and administered either chitosan-pectin based matrix of levodopa/carbidopa, Sinemet® CR or levodopa/carbidopa immediate release powder. Rats were administered the different formulations of levodopa/carbidopa (20/5 mg/kg) per os every 12 hours. The pharmacokinetic parameters of levodopa were estimated for the various treatment groups. The percentage content of levodopa and carbidopa in the various formulations was within the acceptance criteria. The AUC0-24 for levodopa/carbidopa multiparticulate matrix (Formulation 3: 484.98 ± 18.70 µg.hr/mL); Formulation 4: 535.60 ± 33.04 µg.hr/mL), and Cmax (Formulation 3: 36.28 ± 1.52 µg/mL; Formulation 4: 34.80 ± 2.19 µg/mL) were higher than Sinemet® CR (AUC0-24 262.84 ± 16.73 µg.hr/mL and Cmax 30.62 ± 3.37 µg/mL). The t 1/2 of the new formulation was longer compared to Sinemet® CR.

Extract of Mallotus oppositifolius (Geiseler) Müll. Arg. increased prefrontal cortex dendritic spine density and serotonin and attenuated para-chlorophenylalanine-aggravated aggressive and depressive behaviors in mice.

Background/Aim: Depression-related aggression is linked to serotonin (5-HT) and dendritic spine alterations. Although Mallotus oppositifolius extract (MOE) has potential for reducing this effect, its specific role remains uncertain. Herein, we evaluated this potential and associated alterations in the brain. Methods: A standard resident-intruder model of para-chlorophenylalanine (pCPA)-induced depression-associated aggression in male ICR mice was used. The resident mice received pCPA (300 mg/kg, i. p.) for 3 consecutive days while saline-treated mice served as negative control. The pCPA aggressive mice were subsequently treated orally with either MOE (30, 100, 300 mg/kg), fluoxetine (20 mg/kg), tryptophan (20 mg/kg) or saline (untreated pCPA group) for 28 days. Locomotor activity was assessed using open field test. Serotonin (5-HT) levels in mice brain and phytochemical fingerprint of MOE were determined by high performance liquid chromatography (HPLC) while gas chromatography-mass spectrometry (GC-MS) was used to identify constituents of MOE. Dendritic spine density and morphology were evaluated using Golgi-Cox staining technique and analyzed with ImageJ and Reconstruct software. Results: Administration of pCPA induced aggressive behavior in mice, evidenced by increased attack behaviors (increased number and duration of attacks), which positively correlated with squeaking and tail rattling. MOE treatment significantly reduced these characteristics of aggression in comparison with vehicle (non-aggressive) and untreated pCPA groups (p < 0.001), and also reduced social exploration behavior. Although the behavioral effects of MOE were comparable to those of fluoxetine and tryptophan, these effects were quicker compared to fluoxetine and tryptophan. Additionally, MOE also markedly increased 5-HT concentration and dendritic spine density in the prefrontal cortex relative to vehicle and untreated pCPA groups (p < 0.05). Interestingly, these behavioral effects were produced without compromising locomotor activity. GC-MS analysis of the MOE identified 17 known compounds from different chemical classes with anti-inflammatory, antioxidant, neuroprotective and antidepressant activities, which may have contributed to its anti-aggressive effect. Conclusion: MOE decreased depression-associated aggressive behavior in mice via increased 5-HT concentration and dendritic spine density in the prefrontal cortex. The MOE-mediated effects were faster than those of fluoxetine and tryptophan. Our finding suggests that MOE may have clinical promise in decreasing aggressive and depressive behaviors.

Gestational iron supplementation reverses depressive-like behavior in post-partum Sprague Dawley rats: Evidence from behavioral and neurohistological studies.

Background: Postpartum depression is a mood disorder that affects about 9-20% of women after child birth. Reports suggest that gestational iron deficiency can cause a deficit in behavioral, cognitive and affective functions and can precipitate depressive symptoms in mothers during the postpartum period. The present study examined the effect of iron supplementation on depressive behavior during postpartum period in a rat model. Method: Female Sprague-Dawley rats were crossed. Pregnant rats received iron, fluoxetine, desferrioxamine or vehicle throughout the period of gestation. During the postpartum period, mothers from all groups were taken through the open field test (OFT), forced swim test (FST), novelty-induced hypophagia (NIH) and sacrificed for histological examination of the brains. Results: Results showed that rats treated with iron-chelating agent, desferrioxamine, and vehicle during gestation exhibited increased immobility scores in the FST, increased latency to feed and reduced feeding in the NIH with corresponding decreased number of neurons and dendritic branches in the cortex of the brain. These depression-related effects were attenuated by perinatal iron supplementation which showed decreased immobility scores in the FST comparable to rats treated with fluoxetine, a clinically effective antidepressant. Iron treatment also decreased latency to feeding while increasing feeding behavior in the NIH. Iron-treated dams had a higher number of neurons with dendritic connections in the frontal cortex compared to vehicle- and desferrioxamine-treated groups. Conclusion: The results suggest that, iron supplementation during gestation exerts an antidepressant-like effect in postpartum Sprague-Dawley rats, attenuates neuronal loss associated with depression and increases dendritic spine density.

Development and In Vitro Evaluation of Oral Capsules from Antiaris: A Convenient Substitute for Peripheral Neuropathy.

Antiaris is a monoherbal decoction produced by the Centre for Plant Medicine Research (CPMR), Mampong-Akuapem, Ghana. It is prepared from the stem bark of Antiaris africana Engl. (Moraceae), prescribed, and dispensed to patients for the management of nervous disorders. This current formulation presents notable challenges in patients' adherence to treatment regimen due to its bulkiness and bitterness. These challenges have resulted in a decrease in therapeutic outcome. This study sought to transform Antiaris into oral capsules to mask its bitter taste and reduce bulkiness of the product to improve patients' convenience. In this study, four (4) conventional release capsule formulations were successfully prepared from the decoction via wet granulation using corn starch, lactose, light magnesium carbonate (LMC), and microcrystalline cellulose (MCC) and labelled A01, A02, A03, and A04 respectively. The drug-excipient compatibility studies on A01, A02, A03, and A04 were investigated using Fourier transform infrared (FTIR) spectroscopy. The flow properties of the granules as well as the quality assessment of the formulations such as dissolution, disintegration, uniformity of weight, and assay tests were evaluated using pharmacopoeial and nonpharmacopoeial methods. Appropriate models were used to investigate the difference factor (f 1 ) and similarity factor (f 2 ) of the dissolution profiles of the formulations and Antiaris. From the study, all formulated granules had excellent flow properties with Carr's index from 7.83 to 9.56%, Hausner's ratio from 1.09 to 1.10, and angle of repose from 25.13 to 27.87°. Drug-excipient compatibility studies demonstrated no interaction between extract and used excipients. All formulations passed the uniformity of weight, disintegration, assay, and dissolution tests. Formulation A02 had the highest dissolution efficiency of 100.12%, while A03 recorded the least value of 97.22% in the 1 h dissolution studies. A comparison of their various dissolution profiles, respectively, to that of its decoction demonstrated their similarity, since, in all comparisons, f 2 < 15 and f 1 > 50. This implies that, any of these four formulations could be a good substitute for Antiaris.

Effect of Metaswitch® dietary supplement on anthropometric parameters, serum lipids, glucose level, oxidative stress and in vivo antioxidant properties in high fat diet-induced overweight Sprague Dawley rats.

PURPOSE: Obesity and overweight are metabolic disorders associated with oxidative stress, and risk factors for many chronic diseases. We sought to investigate the effects of Metaswitch dietary supplement on weight gain and associated acute metabolic alterations in a high-fat diet-induced overweight rat model. METHODS: Female Sprague Dawley (SD) rats were put into 6 groups. Control groups were fed normal (NCD) or high-fat diet (HFD). Treatment groups on HFD receieved 3 different daily doses of Metaswitch for 3 weeks. Another group on HFD received Slimrite® (phenylpropanolamine), a standard drug. Rats on HFD also received cyproheptadine to stimulate appetite. Food consumption and anthropometric parameters were determined weekly. Serum lipids, glucose level, hepatic lipid peroxidation, and antioxidant activity were used to assess overweight in rats. RESULTS: Food intake remained relatively constant among groups. Rats on HFD had significantly increased body weight compared to rats fed NCD. Metaswitch significantly prevented weight gain; this effect was greater or similar to rats administered Slimrite, but was not dose-dependant. No significant changes occurred in the levels of serum lipids and glucose among the groups. However, serum triglyceride (TG) was significantly increased. The TG/HDL-C ratio revealed significant metabolic alterations which was prevented by Metaswitch. Catalase activity was significantly decreased in the HFD untreated group but was restored in Metaswitch-treated groups. CONCLUSIONS: A 3-week HFD regimen with cyproheptadine supplementation in female SD rats resulted in a significant increase in body weight and acute metabolic alterations. The aforementioned changes were found to have been prevented with the administration of Metaswitch.

Approaches for the Elimination of Microbial Contaminants from Lippia multiflora Mold. Leaves Intended for Tea Bagging and Evaluation of Formulation.

Elimination of microorganisms from herbal products has been a major concern due to its implicated health risk to consumers. Drying of herbal materials has been employed for centuries to reduce the risk of contamination and spoilage. The present study adopted three drying approaches in an attempt to eliminate microorganisms from Lippia multiflora tea bag formulation. This study also evaluated the tea bags and optimized the extraction procedure. The L. multiflora leaves for tea bagging were air-dried and milled (A), oven-dried and milled (B), and microwaved (the milled air-dried leaves) (C). The moisture contents were determined at 105°C ± 2°C for 2 hours to constant weight. Phytochemical parameters such as phytochemical constituents, total water extractive, and pH were assessed. The microbial safety and quality of the L. multiflora tea bags were evaluated using the British Pharmacopoeia 2019 specifications. The uniformity of the mass of the formulated tea bags was also determined. Extraction from the Lippia tea bags was optimized. The results showed that using the approaches (A, B, and C) adopted for drying and processing, the moisture contents of the formulated tea bags were in the range of 9.75-10.71% w/w. All the formulated tea bags contained reducing sugars, phenolic compounds, polyuronides, flavonoids, anthracenosides, alkaloids, saponins, and phytosterols. The pH range of the formulations was 7.11-7.54, whereas the total water extractive values were in the range of 19.12-20.41% w/w. The one-way analysis of variance demonstrated no significant difference in the data obtained from the results from A, B, and C. The formulation from A was found to be unsafe for consumption due to unacceptable microbial contamination limits. Microbial load of the formulations from B and C were within the BP specifications. All the batches of the formulations passed the uniformity of mass test. An optimized extraction procedure was obtained when one tea bag was extracted in 250 mL of hot water within the specified time. L. multiflora leaves meant for tea bagging should be oven-dried or microwaved before tea bagging for safe consumption.

A review on anti-peptic ulcer activities of medicinal plants used in the formulation of Enterica, Dyspepsia and NPK 500 capsules.

Peptic ulcer disease affects many people globally. With the increasing resistance to some orthodox antibiotics such as Clarithromycin and Metronidazole, it is important that new acceptable, safer and effective therapies are developed to manage this disease. Various herbal medicines have been used traditionally for the remedy of peptic ulcer disease (PUD), however scientific information with regards to their anti-peptic ulcer both in-vivo and in-vitro as well as clinical studies supporting their use is still inadequate. The Centre for Plant Medicine Research, (CPMR) Mampong-Akuapem, Ghana manufactures three herbal Products namely Enterica, Dyspepsia and NPK 500 capsules which are currently used for the remedy of PUD as a triple therapy at its out-patient clinic with promising effects. The aim of this review is to gather information from literature on the anti-ulcer properties, pharmacological, phytochemical constituents and related activities of herbal plants used at the CPMR for formulation of the triple herbal therapy. This review may, provide some scientific bases for the use of Enterica, Dyspepsia and NPK 500 capsules in the management of Peptic ulcer at the CPMR out-patient clinic. METHODS: Organization for the review involved the on and/or offline search for information from available literature using electronic data and scientific research information resources such as PubMed, Science Direct and Google scholar. RESULTS: In this review, fifteen ethno-medicinal plants used for the formulation of Enterica, Dyspepsia and NPK capsules have been discussed, presenting the description of the plants, composition and pharmacological activity. INTERPRETATION: Tables with the summary of reviewed medicinal plants with their anti-ulcer models and inference on possible mechanisms of action were drawn up. The mechanism(s) of action of individual plants and products (Enterica, Dyspepsia and NPK 500 capsules) must be further investigated and established experimentally in-vitro in addition to in-vivo pharmacological and clinical activity studies to confirm their use in the remedy of PUD.

Strategies for formulation of effervescent granules of an herbal product for the management of typhoid fever.

Herbal medicines are currently being adopted as alternatives to orthodox medicines for the management of drug-resistant and emerging multidrug-resistant microbial strains of various diseases, including typhoid fever. A herbal decoction, MA 001, manufactured by the Centre for Plant Medicine Research (CPMR), has been used for the treatment of typhoid fever for at least two decades in Ghana with desirable outcomes. MA 001 is formulated from Citrus aurantifolia, Spondias mombin, Latana camara, Bidens pilosa, Trema occidentalis, Psidium guajava, Morinda lucida, Vernonia amygdalina, Persea americana, Paulina pinnatta, Momordia charantia and Cnestis ferruguinea medicinal plants. The low palatability and compliance to treatment due to the bulky nature of the decoction poses challenges in its optimum use. This study sought to design and formulate the therapeutic components of the aqueous herbal decoction of MA 001 into an optimal solid dosage form of effervescent granules to improve the delivery of MA 001 as well as increase patient compliance and convenience of product handling. The methods involved pre-formulation studies on the suitability of effervescent vehicles, formulation and evaluation of effervescent granules for drug excipient interactions using high performance liquid chromatography analysis. The findings indicate that the effervescent granules were suitable for use in the delivery of the therapeutic constituents for the treatment of typhoid fever as done with the decoction due to minimal herbal extract-excipient interaction.

A Pharmacokinetic Evaluation of a Pectin-Based Oral Multiparticulate Matrix Carrier of Carbamazepine.

BACKGROUND: Carbamazepine is a drug used in the treatment of neurological disorders such as epilepsy. However, due to its erratic absorption, oral bioavailability is often poor. There is, therefore, the need to develop alternative formulations for carbamazepine with better pharmacokinetic characteristics. AIM: The aim of this study was to formulate an oral modified-release multiparticulate matrix of carbamazepine from cocoa pod husk (CPH) pectin and evaluate the pharmacokinetic profile of this formulation using in vitro and in vivo models. METHODS: CPH pectin was extracted from cocoa pod husks with hot aqueous and citric acid solutions. Oral multiparticulate carbamazepine matrices were formulated from CPH pectin cross-linked with calcium. The formulation was evaluated for carbamazepine content and release profile in vitro. For in vivo pharmacokinetic profile estimation, rats were put into 4 groups of 5 animals each to receive carbamazepine multiparticulate matrix formulations A and B, carbamazepine powder, and Tegretol CR®. Animals in each group received 200 mg/kg of each drug via the oral route. Maximum plasma concentration (C max), area under the concentration-time curve (AUC), elimination rate constant (K e ), and terminal half-life (t 1/2) of the formulations were estimated by noncompartmental analysis. RESULTS: The pectin extraction from fresh cocoa pod husks using hot aqueous and citric acid solutions gave pectin yields of 9.63% and 11.54%, respectively. The drug content of carbamazepine in CPH pectin formulations A and B was 95% and 96%, respectively. There was controlled and sustained release of carbamazepine for both formulations A and B in vitro. AUC0⟶36 (176.20 ± 7.97 µg.h/mL), C max (8.45 ± 0.71 µg/mL), T max (12 ± 1.28 h), and t 1/2 (13.75 ± 3.28 h) of formulation A showed a moderately enhanced and comparable pharmacokinetic profile to Tegretol CR® (AUC0⟶36: 155 ± 7.15 µg.h/mL, C max: 8.24 ± 0.45 µg/mL, T max: 8.0 ± 2.23 h, and t 1/2: 13.51 ± 2.87 h). CONCLUSION: Findings from the study suggest that formulations of CPH pectin had the potential to control and maintain therapeutic concentrations of carbamazepine in circulation over a period of time in the rat model.

Formulation and In Vitro Evaluation of Oral Capsules and Suspension from the Ethanolic Extract of Cola nitida Seeds for the Treatment of Diarrhea.

Management of diarrhea has evolved over the years from relatively inadequate interventions in the early years to more successful physiological approaches. The use of herbal medicinal products and supplements has grown significantly over the past three decades, with more than half of the global population depending on it for some aspect of their primary health care needs. This study is aimed at formulating solid and liquid oral dosage forms of the ethanolic extract of Cola nitida seeds for the treatment of diarrhea. The flow property of the dried ethanolic extract was determined and subsequently formulated into granules for encapsulation. The ethanolic extract was also used in formulating an oral suspension. Pharmacopeia tests such as uniformity of weight, disintegration, drug content, and dissolution were carried out on the formulated capsules. The formulated suspension was also assessed using the following parameters; viscosity, flow rate, drug content, dissolution, sedimentation rate, and sedimentation volume. The dried ethanolic extract and formulated granules exhibited good flow properties. The formulated capsules exhibited optimal in vitro release of extract (>90% after 45 minutes) and passed the uniformity of weight, disintegration, and drug content tests. The formulated suspension also passed the drug content test and had a good sedimentation rate, sedimentation volume, and flow rate. The formulated suspension also exhibited pseudoplastic flow, optimal viscosity, and a good in vitro release profile (>90% after 45 minutes). Capsules and suspension of the ethanolic extract of Cola nitida seeds have been successfully formulated and can be used as standard dosage forms for the management of diarrhea.

Managing Vibrio cholerae with a local beverage: preparation of an affordable ethanol based hand sanitizer.

Research indicates an increased use of hand sanitizers globally, and in particular developing countries where bacterial epidemics such as cholera are common. While there is evidence of availability, high demand and use of hand sanitizers, the incidence of cholera in developing countries remains unabated. Several reasons have been put forward, and cost of hand sanitizers remains dominant. It is in response to this contradictory situation of availability but limited access, that this study was conducted to present an alternative option of formulating a high quality and cost effective ethanol-based sanitizer from a Ghanaian local beverage (akpeteshie). The concentration of ethanol in akpeteshie was determined using gas chromatography. An Ethanol based hand sanitizer (Sample C) was formulated with akpeteshie and tested against Vibrio cholerae using the microbial time -kill kinetics assay. Commercially available ethanol based Equi-Clean hand sanitizer (62%) (Sample D) was used as the standard. Results show that the akpeteshie contained 73.08% ethanol and formulated product (Sample C) contained 63.70% ethanol. Viscosity and pH of Sample C were; 89 rpm (1.48 cps) and 7.30 respectively whiles that of Sample D were; 80 rpm (1.33 cps) and 7.50 respectively. The formulated product (Sample C) was effective against Vibrio cholerae with a gradual reduction in microbial count upon exposure to the organisms at time intervals of 0, 5, 15, 30, 60 and 120 min.

Potential of Cocoa Pod Husk Pectin-Based Modified Release Capsules as a Carrier for Chronodelivery of Hydrocortisone in Sprague-Dawley Rats.

The potential of cocoa pod husk (CPH) pectin-based modified release (MR) capsules as a carrier for chronodelivery of hydrocortisone in Sprague-Dawley rats was assessed. Extemporaneously formulated CPH pectin-based hydrocortisone (10 mg) capsules crosslinked with calcium chloride (Formulation A) or zinc (Formulation B) and a commercial immediate release hydrocortisone formulation were administered orally to Sprague-Dawley rats and the pharmacokinetic parameters were evaluated using noncompartmental analysis. Formulation A had a 2 h lag phase followed by an increase in serum drug concentration in the treated rats. Peak concentrations (Cmax) of 21.799 ± 1.993 ng/ml and 20.844 ± 2.661 ng/ml were achieved after 6 ± 0.23 h and 6 ± 0.35 h (Tmax), respectively, for capsules A and B. The immediate release formulation had a peak concentration of 15.322 ± 0.313 ng/ml within 1 ± 0.2 h. The relative bioavailability of the CPH pectin-based capsules A and B was 213% and 274%, respectively. Formulations A and B had half-lives more than three times that of the immediate release formulation. The MR capsules exhibited a higher exposure, greater bioavailability, and versatility in release of cortisol than the commercial immediate release formulation. Additionally, the MR capsules exhibited an extended drug release with overnight cortisol rise and early morning cortisol peak and hold promise in the management of adrenal insufficiency.

Quality Assessment of Some Essential Children's Medicines Sold in Licensed Outlets in Ashanti Region, Ghana.

The quality of 68 samples of 15 different essential children's medicines sold in licensed medicine outlets in the Ashanti Region, Ghana, was evaluated. Thirty-two (47.1%) of the medicines were imported, mainly from India (65.6%) and the United Kingdom (28.1%), while 36 (52.9%) were locally manufactured. The quality of the medicines was assessed using content of active pharmaceutical ingredient (API), pH, and microbial limit tests, and the results were compared with pharmacopoeial standards. Twenty-six (38.2%) of the samples studied passed the official content of API test while 42 (61.8%) failed. Forty-nine (72.1%) of the samples were compliant with official specifications for pH while 19 (27.9%) were noncompliant. Sixty-six (97.1%) samples passed the microbial load and content test while 2 (2.9%) failed. Eighteen (26.5%) samples passed all the three quality evaluation tests, while one (1.5%) sample (CFX1) failed all the tests. All the amoxicillin suspensions tested passed the three evaluation tests. All the ciprofloxacin, cotrimoxazole, flucloxacillin, artemether-lumefantrine, multivitamin, and folic acid samples failed the content of API test and are substandard. The overall API failure rate for imported products (59.4%) was comparable to locally manufactured (63.9%) samples. The results highlight the poor quality of the children's medicines studied and underscore the need for regular pharmacovigilance and surveillance systems to fight this menace.

Cocoa Pod Husk Pectin Intended as a Pharmaceutical Excipient Has No Adverse Effects on Haematological Parameters in Sprague Dawley Rats.

Natural polymer research has recently become the focus of intensive research in the quest for new enabling excipients for novel drugs in pharmaceutical formulation for optimal treatment outcomes. Evaluations of some excipients have shown deleterious haematological effects of varying extents on the safety profile of these excipients. A 90-day subchronic toxicity study was conducted to evaluate the influence of cocoa pod husk (CPH) pectin on indicators for haematotoxicity. Male and female Sprague Dawley rats (SDRs) were fed with CPH pectin in doses up to 71.4 mg/kg. The effects of CPH pectin on the haematological indices, direct and total bilirubin, and the spleen were determined. The results indicated that CPH pectin did not induce any untoward toxic effects on the haematological indices, bilirubin levels, and the spleen. There were, however, elevations in MCV at day 30, which was not sustained after the 90 days. The data obtained from this study did not reveal any remarkable findings of toxicological relevance to the haematopoietic system.

Novel HPLC Analysis of Hydrocortisone in Conventional and Controlled-Release Pharmaceutical Preparations.

An isocratic sensitive and precise reverse phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the determination and quantification of hydrocortisone in controlled-release and conventional (tablets and injections) pharmaceutical preparations. Chromatographic separation was achieved on an ODS (C18), 5 µm, 4.6 × 150 mm, with an isocratic elution using a freshly prepared mobile phase of composition methanol : water : acetic acid (60 : 30 : 10, v/v/v) at a flow rate of 1.0 ml/min. The detection of the drug was successfully achieved at a wavelength of 254 nm. The retention time obtained for the drug was 2.26 min. The proposed method produced linear detectable responses in the concentration range of 0.02 to 0.4 mg/ml of hydrocortisone. High recoveries of 98-101% were attained at concentration levels of 80%, 100%, and 120%. The intraday and interday precision (RSD) were 0.19-0.55% and 0.33-0.71%, respectively. A comparison of hydrocortisone analyses data from the developed method and the official USP method showed no significant difference (p > 0.05) at a 95% confidence interval. The method was successfully applied to the determination and quantification of hydrocortisone in six controlled-release and fifteen conventional release pharmaceutical preparations.

In Vitro Evaluation of Cocoa Pod Husk Pectin as a Carrier for Chronodelivery of Hydrocortisone Intended for Adrenal Insufficiency.

This study evaluated the in vitro potential of cocoa pod husk (CPH) pectin as a carrier for chronodelivery of hydrocortisone intended for adrenal insufficiency. FTIR studies found no drug-CPH pectin interactions, and chemometric analysis showed that pure hydrocortisone bears closer similarity to hydrocortisone in hot water soluble pectin (HWSP) than hydrocortisone in citric acid soluble pectin (CASP). CPH pectin-based hydrocortisone matrix tablets (~300 mg) were prepared by direct compression and wet granulation techniques, and the tablet cores were film-coated with a 15% HPMC formulation for timed release, followed by a 12.5% Eudragit® S100 formulation for acid resistance. In vitro drug release studies of the uncoated and coated matrix tablets in simulated gastrointestinal conditions showed that wet granulation tablets exhibit greater retardation of drug release in aqueous medium than directly compressed tablets. CASP showed greater suppression of drug release in aqueous medium than HWSP. Wet granulation HWSP-based matrix tablets coated to a final coat weight gain of ~25% w/w were optimized for chronodelivery of hydrocortisone in the colon. The optimized tablets exhibited a lag phase of ~6 h followed by accelerated drug release in the colonic region and have potential to control night time cortisol levels in patients with adrenal insufficiency.

Physicochemical and Antimicrobial Properties of Cocoa Pod Husk Pectin Intended as a Versatile Pharmaceutical Excipient and Nutraceutical.

The physicochemical and antimicrobial properties of cocoa pod husk (CPH) pectin intended as a versatile pharmaceutical excipient and nutraceutical were studied. Properties investigated include pH, moisture content, ash values, swelling index, viscosity, degree of esterification (DE), flow properties, SEM, FTIR, NMR, and elemental content. Antimicrobial screening and determination of MICs against test microorganisms were undertaken using agar diffusion and broth dilution methods, respectively. CPH pectin had a DE of 26.8% and exhibited good physicochemical properties. Pectin had good microbiological quality and exhibited pseudoplastic, shear thinning behaviour, and high swelling capacity in aqueous media. The DE, FTIR, and NMR results were similar to those of previous studies and supported highly acetylated low methoxy pectin. CPH pectin was found to be a rich source of minerals and has potential as a nutraceutical. Pectin showed dose-dependent moderate activity against gram positive and gram negative microorganisms but weak activity against Listeria spp. and A. niger. The MICs of pectin ranged from 0.5 to 4.0 mg/mL, with the highest activity against E. coli and S. aureus (MIC: 0.5-1.0 mg/mL) and the lowest activity against A. niger (MIC: 2.0-4.0 mg/mL). The study has demonstrated that CPH pectin possesses the requisite properties for use as a nutraceutical and functional pharmaceutical excipient.