The Pharma Innovation Journal 2015; 3(11): 78-81

ISSN: 2277- 7695

TPI 2015; 3(11): 78-81
© 2015 TPI
Formulation and evaluation of floating
www.thepharmajournal.com
Received: 15-12-2015
gastroretentive capsules of acyclovir with piperine
Accepted: 15-01-2015 as a bioenhancer
Smriti Khatri
RamEesh Institute of Vocational
and Technical Education, Smriti Khatri, Farhan Jalees Ahmed, Pallavi Rai
Greater Noida, Uttar Pradesh, Pin
Code: 201310, India. Abstract
The aim of the present investigation was to develop and evaluate the sustained release hydrodynamic
Farhan Jalees Ahmed balanced systems for acyclovir using hydrocolloid polymers such as hydroxy propyl methylcellulose
Professor, Department of
(HPMC) and ethyl cellulose (EC). Floating was achieved by adding an effervescent mixture of sodium
pharmaceutics, Jamia Hamdard,
bicarbonate and anhydrous citric acid. The best formulation was selected based on in vitro characteristics
New Delhi, India.
and further in vivo studies were carried out on Sprague Dawley strain rats to evaluate the bioavailability
Pallavi Rai of the drug. Nearly two times higher Area under the curve (AUC) was observed as compared to the drug
RamEesh Institute of Vocational solution. In addition, Acyclovir formulation showed the ability to maintain the acyclovir plasma
and Technical Education, concentration through 24 hr as compared to the drug solution that could maintain this level of drug only
Greater Noida, Uttar Pradesh, Pin for 4 hr.
Code: 201310, India.
Keywords: Acyclovir, Hydroxyl propyl methyl cellulose, Piperine, Floating Drug Delivery System

1. Introduction
Bioenhancers` are the agents, which, when combined with an active drug lead to the
potentiation of the pharmacological effect due to increase in the bioavailability of the drug.
One such example is piperine, an alkaloid obtained from Piper nigrum. Piperine has the ability
to increase drug bioavailability by increasing the blood supply to the gastrointestinal tract,
decreasing hydrochloric acid secretion which prevents breakdown of some drugs, increasing
emulsifying content of the gut, increasing enzymes like gamma-glutamyl transpeptidase which
participate in active and passive transport of nutrients to the intestinal cells, and inhibiting
enzymes participating in biotransformation of drugs, preventing their inactivation and
elimination [1]. Another rationale approach to enhance bioavailability and improve
pharmacokinetics and pharmacodynamic profiles is to retain the drug reservoir above its
absorption area, i.e. in the stomach and to release the drug in a controlled manner, so as to
achieve zero order kinetics for a prolonged period of time. Thus, one of the most feasible
approaches for achieving a prolonged and predictable drug delivery profile is to control the
gastric residence time in GIT [2, 3]. Gastro retentive dosage forms significantly extend the
period of time over which drugs may be released and prolong dosing intervals which may
increase patient compliance. Such systems are more advantageous in improving
gastrointestinal absorption of drugs with narrow absorption windows as well as for controlling
the release of the drugs having site-specific absorption limitation [4-6]. Retention of drug
delivery systems in the stomach prolongs the overall GI transit time, thereby resulting in
improved bioavailability for some drugs [7]. The controlled gastric retention of solid dosage
forms may be achieved by the mechanisms of mucoadhesion, floatation, sedimentation,
expansion, modified shape systems, or by the simultaneous administration of pharmacological
agents that delay gastric emptying [8, 9]. Floating drug delivery offers several applications for
drugs having poor bioavailability because of the narrow absorption window in the upper part
of the gastrointestinal tract [10, 11]. It retains the dosage form at the site of absorption and thus
enhances the bioavailability [12, 13]. Acyclovir [9-(2-hydroxyethoxymethyl) guanine] is an
Correspondence: acyclic nucleoside analogue of guanosine that is a potent and selective antiviral agent.
Smriti Khatri Acyclovir has a relatively short plasma half-life of 3 hrs. The aim of the present study was to
RamEesh Institute of Vocational
develop a hydro-dynamically balanced system of acyclovir with piperine [14] as single-unit
and Technical Education,
Greater Noida, Uttar Pradesh, floating capsules.
Pin Code: 201310, India.

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2. Material and Method low-density polymers, which upon administration would attain
Acyclovir and Hydroxypropyl Methylcellulose (HPMC) K4M a density of less than that of the gastric fluids and therefore
were obtained as a gift sample from M/s Ranbaxy Research would float. Exactly 200 mg of acyclovir was weighed and
Laboratories (Gurgaon, India). Piperine was purchased from physically blended with polymers in a glass mortar and pestle
Sigma Chem. Ltd., New Delhi. All other chemicals and and filled in a hard gelatin capsule # 0. The drug and polymer
reagents used were of analytical grade. blend was transferred into the empty capsule shells manually.
The polymer and drug mixture was blended for 10 minutes in a
2.1 Preparation of Capsules double cone blender. The composition of the HBS capsules is
Single-unit capsules were formulated with the help of different given in Table 1.

Table 1: Formulae of Acyclovir capsules with Piperine

Ingredients M1 M2 M3 M4 M5 M6 M7 M8 M9 M10
Acyclovir 200 mg 200 mg 200 mg 200 mg 200 mg 200 mg 200 mg 200 mg 200 mg 200 mg
HPMCK4M 150 200 250 300 350 400
Ethyl Cellulose 50 100 150 200
Sodium bicarbonate 10 20 30 40 50 50 50 50 50 50
Piperine 40 40 40 40 40 40 40 40 40 40
Succinic Acid 10 15 20 25 30 30 30 30 30 30

2.2 Evaluation of capsules [15-18] 2.2.6 Kinetics of Drug Release

The capsules were evaluated for various parameters as The dissolution profile of all the batches was fitted to zero
follows: order kinetics, first order kinetics, Higuchi, Hixon-Crowell,
Korsmeyer and Peppas equation to ascertain the kinetic
2.2.1 Appearance and Shape modeling of drug release by using a PCP Disso Version 2.08
The general appearance of the capsules includes the software, and the model with the highest correlation
morphological characteristics like size, shape, colour, etc. coefficient was considered to be the best fit model.
2.2.2 Weight Variation/uniformity of weight 2.2.7 Pharmacokinetic study of acyclovir floating capsules
To study weight variation, 20 capsules of each formulation with piperine [20]
were weighed using an electronic balance and the test was Rats (Sprague Dawley strain), 6 to 8 months old, weighing
performed as per I.P. 200–220 g were divided into four groups, each consisting of
six animals. The protocols for these investigations were
2.2.3 Uniformity of content approved by the Institutional Animal ethics committee in
Five capsules were weighed and their contents were removed. accordance with the disciplinary principles and guidelines of
An accurately weighed sample equivalent to 100 mg of CPCSEA (registration no 723/02/a/CPCSEA). Rats were kept
Acyclovir was taken in a stoppered volumetric flask (100 ml). on fasting 12 h before drug administration and until 24 h post
The content was dissolved in 0.1 N HCl and the volume made dosing. Water was provided ad libitum throughout the study.
up to 100 ml. This solution was filtered through Whatman The first group received an oral administration of 0.1 %
filter paper No. 41. The solution was diluted and the sodium CMC suspension (normal control). The second group
absorbance was measured at 254 nm. The drug content was received an oral administration of 4 % drug solution in sodium
calculated. CMC suspension. An accurately weighed sample of floating
2.2.4 In vitro Buoyancy Study [19] capsules equivalent to 40 mg of acyclovir were suspended in
All formulations were subjected to buoyancy test. Buoyancy 0.1 % sodium CMC suspension and administered orally using
test was done using USP type II apparatus at 50 rpm a feeder tube under non-anesthetic condition. At 1, 2, 4, 8, 12
maintained at 37±0.5 °C. Capsules were placed in 900 ml jar and 24 h time intervals, blood samples were collected from the
containing 0.1N HCl as dissolution medium. The amount of jugular vein in Eppendorf tubes and centrifuged at 3000 rpm
time during which the capsules remained buoyant was the for 10 min (REMI Equipment, Mumbai, India). Supernatant
floating time. The polymer that showed the best floating was collected and filtered through a 0.45 μm filter into
behavior was used for in vitro release studies. volumetric flask and drug concentration was determined by
LCMS method.
2.2.5 Dissolution Studies
The release rate of acyclovir from floating matrix capsules 3. Result and Discussion
(n=3) was determined using USP dissolution test apparatus 3.1 Weight variation
Type II. The dissolution test was performed using 900 ml of The average weight of capsules within each formulation was
0.1N HCl at 50 rpm. The temperature of the medium was found to be uniform. This indicates uniform filling of powder
maintained at 37±0.5 ºC and the study was carried out for 12 blend during capsule filling. Not more than two of the
hrs. Aliquot of 5 ml was withdrawn at an interval of 30 min, 1 individual weights deviated from the average weight by more
hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 hr and 12 hr respectively. The than 7.5% and none deviated by more than twice that
withdrawn samples were replaced with fresh dissolution percentage, which provided good weight uniformity.
medium. The samples were filtered through Whatman filter
paper (No. 41) and the volume made up to 10 ml with 0.1N 3.2 Drug content
HCl. The samples were analyzed at 254 nm. In all the ten formulations, the values for drug content were
found to be uniform among different batches of the

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Hydrodynamic Balance System and ranged between 98.3 and 3.5 Kinetics of drug release
102.7% of the theoretical value. The value ensured the The in vitro release from the optimized formulation was fitted
uniformity of the drug content in the capsules. to kinetic release models (PCP Disso v3) and it was concluded
that the drug release from the formulation followed a zero
3.3 In vitro buoyancy study of the capsules [21-24] order, as the R2 value for zero order was 0.995 as compared to
The initial batches of M1 and M2 prepared with less amount of the R2 value for first order release was 0.959. Further the zero
sodium bicarbonate did not show any sign of floating. order release was supported by good R2 value by fitting the in
Therefore, sodium bicarbonate was used as a gas-generating vitro release into Higuchi model i.e. 0.932. Thus, it could be
agent in order to float the capsule. The sodium bicarbonate concluded that the drug release from the formulation is
generates carbon dioxide in the presence of dissolution diffusion controlled.
medium (0.1 N HCl).
The gas generated was trapped and protected within the gel 3.6 Pharmacokinetic parameters of different formulations
formed by hydration of the polymer, thus decreasing the containing acyclovir after oral administration.
density of the capsule below 1 gm/mL, and the capsule became The formulation of acyclovir with piperine showed superiority
buoyant. Succinic acid was incorporated in the formulation over the other formulations. Nearly two times higher AUC0–
batches to nullify the effect of the acidic dissolution media on 24 value of acyclovir for these capsules (14614.13±6953.13 ng
the drug release. No formulation from batches M7 to M10 h/ml) as compared to drug solution (7552.33±3219.09 ng
containing Ethyl Cellulose showed floating because the h/ml) was observed. In addition, Acyclovir formulation
formulation did not swell and hence failed to form a gel. The showed the ability to maintain the acyclovir plasma
formulation M6 containing drug and polymers in the ratio of concentration through 24 h as compared to the drug solution
50:50 remained buoyant in 0.1 N HCl for more than 12 h and that could maintain this level of drug only for 4 h.
maintained the shape as shown in figure 1. So this
combination was selected for further study 4. Conclusion
The results obtained, confirmed the sustained release potential
of floating capsules of acyclovir with piperine prepared from
HPMC K4M polymer. Hence, the overall better
pharmacokinetics performance of the floating
Hydrodynamically balanced system of acyclovir with piperine
in comparison to drug solution is due to increased residence
time within the upper GI tract as evident by the GI distribution
study as well as due to piperine as a bioenhancer.

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